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During an earlier multicenter, open-label, randomized controlled trial designed to evaluate the effectiveness of high-dose inhaled ciclesonide in patients with asymptomatic or mild coronavirus disease 2019 (COVID-19), we observed that worsening of shadows on CT without worsening of clinical symptoms was more common with ciclesonide. The present study sought to determine if an association exists between worsening CT shadows and impaired antibody production in patients treated with inhaled ciclesonide. Eighty-nine of the 90 patients in the original study were prospectively enrolled. After exclusions, there were 36 patients each in the ciclesonide and control groups. We analyzed antibody titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein at various time points. Changes in viral load during treatment were compared. There was no significant difference in age, sex, body mass index, background clinical characteristics, or symptoms between the two groups. Although evaluation on day 8 suggested a greater tendency for worsening shadows on CT in the ciclesonide group (p = 0.072), there was no significant difference between them in the ability to produce antibodies (p = 0.379) or the maximum antibody titer during the clinical course. In both groups, worsening CT shadows and higher viral loads were observed on days 1-8, suggesting ciclesonide does not affect clearance of the virus (p = 0.134). High-dose inhaled ciclesonide did not impair production of antibodies against SARS-CoV-2 or affect elimination of the virus, suggesting that this treatment can be used safely in patients with COVID-19 patients who use inhaled steroids for asthma and other diseases.

Background: Ciclesonide (CIC) is an inhaled corticosteroid (ICS) approved for the maintenance treatment of asthma in patients ages ≥ 12 years. The prodrug aspect of CIC is associated with a safety profile that may make it ideal for children. Objective: The objective was to summarize efficacy results from the eight phase III, randomized, double-blind, controlled trials in children with asthma conducted during CIC clinical development. Methods: Four trials compared CIC 40, 80, or 160 µg/day with placebo. Two trials compared CIC 160 µg/day with fluticasone propionate 200 µg/day, one trial compared CIC 80 or 160 µg/day with fluticasone 200 µg/day, and one trial compared CIC 160 µg/day with budesonide 400 µg/day. Results: The primary end point was met by at least two CIC doses versus placebo in the trials in which the primary end point was the change from baseline in lung function outcome (forced expiratory volume in 1 second [FEV 1 ] % predicted or morning peak expiratory flow [PEF]). A trial that compared CIC with placebo did not meet the primary end point of superiority in time-to-first severe wheeze exacerbation or lack of improvement. The primary end point of noninferiority to the active control (fluticasone or budesonide) in the change from baseline in a lung function outcome (FEV 1 , morning PEF, evening PEF) was met with the CIC 160-µg dose in all active control trials. CIC generally demonstrated statistically significant improvements in forced expiratory flow at 25%-75% of forced vital capacity, asthma symptoms, rescue medication use, and asthma control when compared with placebo and noninferiority for these outcomes compared with fluticasone or budesonide. Conclusion: In children with asthma, once-daily CIC significantly improved large and small airway function, asthma symptoms, and asthma control, and reduced rescue medication use compared with placebo. CIC was comparable with other ICS used to treat asthma in children, which demonstrated its worth for the pediatric population.

The principal objective of this research has been to determine the safety of inhaled glucocorticoids (GCs) in respect of their effect on CD8 + T cells within respiratory and extra-respiratory tissues, and to compare it with systemic GC treatment. Another purpose has been to identify whether inhaled and systemic GCs affect the CD8 + T cell response in the mediastinal lymph nodes (MLNs) and lungs in a mouse model of ovalbumin (OVA)-induced asthma. Ciclesonide and methylprednisolone were used as a model for inhaled and systemic GCs, respectively. The CD8 + T cell response was observed in untreated OVA-immunized mice, manifesting itself by the proliferation of these cells and their recruitment into the lower respiratory tract. Inhaled and systemic GC treatment fully prevented this response. This suggests that one of the elements contributing to the anti-asthmatic efficacy of inhaled and systemic GCs could be the inhibition of the effector CD8 + T cell response which accompanies the disease. The anti-asthmatic effect of GCs was rather not mediated through the generation or/and increased recruitment of Foxp3 + CD25 + CD8 + regulatory T cells into the MLNs and lungs. Inhaled and systemic GCs produced comparable depletions of normal CD8 + T cells in the MLNs, the head and neck lymph nodes and in peripheral blood, and this effect, at least to some extent, resulted from the proapoptotic action of GCs towards these cells. These results suggest that inhaled GC therapy might not be safer at all than treatment with systemic GCs in respect of the undesirable effects on CD8 + T cells residing within and outside the respiratory tract., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: Many trials have been published comparing inhaled corticosteroid (ICS) treatments in asthma. However, mixed results necessitate the summarization of available evidence to aid in decision-making. Areas covered: This systematic review evaluated randomized controlled trials (RCTs) that compared the efficacy and safety of inhaled fluticasone propionate (FP) with other ICS including beclomethasone dipropionate (BDP), budesonide (BUD) and ciclesonide (CIC). PubMed was searched and 54 RCTs that fit pre-determined criteria were included. Endpoints evaluated included lung function, asthma symptom control, exacerbation frequency, reliever use, quality of life and steroid-related side effects. Expert commentary: Across all studies, FP was associated with either more favorable or at least similar efficacy and safety, in comparison with BDP or BUD. This observation may be related to FP's higher relative potency and almost negligible oral bioavailability. FP was comparable to CIC for efficacy. However, CIC appeared to have a smaller impact on cortisol levels than FP, which is likely due to CIC's incomplete conversion to active metabolite (des-CIC) and the lower potency of des-CIC compared with FP. Although there were no significant differences in evaluated outcomes after treatment with different ICS in the majority of studies, some observed differences could be explained by their respective pharmacodynamic and pharmacokinetic properties.

To achieve a better understanding of mechanisms underlying the anti-asthmatic action of inhaled and systemic glucocorticoids (GCs) and to provide more data regarding the risk of a negative effect of inhaled GCs on CD4 + T cells, a study was conducted on the effect of ciclesonide and methylprednisolone on CD4 + effector (Teff), regulatory (Treg) and resting (Trest) T cells within respiratory and extra-respiratory tissues in a mouse model of allergic asthma. The study indicated that one, and possibly a key mechanism, underlying the anti-asthmatic action of inhaled and systemic GCs is the prevention of the activation and clonal expansion of CD4 + Teff cells in the mediastinal lymph nodes (MLNs), which consequently prevents infiltration of the lungs with CD4 + Teff cells. The beneficial effects of GCs in asthma treatment were not mediated through increased recruitment of Treg cells into the MLNs and lungs and/or local generation of Treg cells. The results demonstrated that inhaled and systemic GCs induced comparable depletion of normal CD4 + Teff, Trest and Treg cells in the MLNs, head and neck lymph nodes and peripheral blood. Furthermore, inhaled, but not systemic GC therapy, led to the loss of these cells in the lungs. Thus, the study suggests that inhaled GC therapy may not be safer at all than systemic one with respect to the adverse effect on CD4 + T cells present within and outside the respiratory tract. Moreover, administration of inhaled GCs can produce negative effects on lung-residing CD4 + T cells., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: This case series intends to highlight the association between decreased linear growth velocity and adrenal suppression in patients receiving inhaled corticosteroids for asthma. A potential treatment option is also discussed. Adrenal suppression secondary to inhaled corticosteroids has previously been reported and is often underrecognized. A decrease in linear height velocity has also been associated with inhaled corticosteroids. However, a decrease in height velocity has not been shown to predict adrenal suppression., Case Study: This case series of 15 patients receiving inhaled corticosteroids for control of asthma were noted to have a decrease in linear growth velocity ultimately associated with adrenal suppression. A change in inhaled corticosteroid to ciclesonide led to recovery of adrenal function without impacting asthma control., Results: Chart review from a pediatric pulmonology clinic was performed. Growth parameters and laboratory studies were recorded and analyzed. A mean decrease in height standard deviation score in the year prior to diagnosis of adrenal suppression was -0.59, -0.11, and -0.18, in pre-puberty, peri-puberty, and post-puberty patients, respectively. After ciclesonide therapy was initiated, a mean change in height standard deviation score of +0.40, +0.13, and -0.13, was noted for pre-puberty, peri-puberty, and post-puberty patients, respectively. A change in growth velocity of +5.3 cm/yr, +2.1 cm/yr, and -1.9 cm/yr, was noted for pre-puberty, peri-puberty, and post-puberty patients, respectively, after starting ciclesonide., Conclusions: Height velocity should be monitored closely during routine asthma visits to identify potential adrenal suppression associated with inhaled corticosteroids use. Ciclesonide is a good option for asthma treatment that allows for adrenal recovery.

Background: Ciclesonide (CIC) is an effective inhaled corticosteroid for treating asthmatic children. However, its effect on airway inflammation assessed by the fraction of exhaled nitric oxide (FENO) in children with persistent asthma is virtually unknown. We aimed to assess the effect of once-daily generic CIC, 80 or 160 μg, on FENO, lung function, asthma control and bronchial hyperresponsiveness, in atopic children with persistent asthma., Methods: This was a 12-week, randomised, double-blind, parallel-group study. Sixty children with mild-to-moderate persistent asthma were recruited. Changes in FENO, asthma control score, lung function (FEV1) and bronchial hyperresponsiveness to methacholine (BHR) were used to assess the effects of both CIC doses. Non-normally distributed variables were log-transformed to approximate normality, and parametric tests were used for comparisons within and between groups at baseline and after 12 weeks of treatment., Results: In the CIC 80 μg group, FENO decreased from 45.0 ppb (95% CI 37.8-53.7) to 32.7 ppb (95% CI 21.0-47.3) at the end of study (P=0.021), whereas in the CIC 160 μg group, FENO decreased from 47.3 ppb (95% CI 40.4-55.3) to 30.5 ppb (95% CI 24.1-38.7) (P<0.001). The difference between groups in FENO at the end of study was not significant (P=0.693). There was a significant improvement of asthma control with both CIC doses but there was no significant change in BHR or FEV1 in either group., Conclusion: Once-daily generic ciclesonide (80 μg or 160 μg), for 12 weeks, is effective to improve airway inflammation and asthma control in atopic children with persistent asthma., (Copyright © 2014 SEICAP. Published by Elsevier Espana. All rights reserved.)

Background: Some patients with refractory asthma have evidence of uncontrolled eosinophilic inflammation in the distal airways. While traditional formulations of inhaled steroids settle predominantly in the large airways, newer formulations with an extra-fine particle size have a more peripheral pattern of deposition. Specifically treating distal airway inflammation may improve asthma control., Methods: 30 patients with refractory asthma despite high dose inhaled corticosteroids were identified as having persistent airway eosinophilia. Following 2 weeks of prednisolone 30 mg, patients demonstrating an improvement in asthma control were randomised to receive either ciclesonide 320 µg twice daily or placebo in addition to usual maintenance therapy for 8 weeks. The primary outcome measure was sputum eosinophil count at week 8. Alveolar nitric oxide was measured as a marker of distal airway inflammation., Results: There was continued suppression of differential sputum eosinophil counts with ciclesonide (median 2.3%) but not placebo (median 4.5%) though the between-group difference was not significant. When patients who had changed their maintenance prednisolone dose during the trial were excluded the difference between groups was significant (1.4% vs 4.5%, p=0.028). Though alveolar nitric oxide decreased with ciclesonide the value did not reach statistical significance., Conclusions: These data demonstrate that patients with ongoing eosinophilic inflammation are not truly refractory, and that suppression of airway eosinophilia may be maintained with additional inhaled corticosteroid. Further work is needed with a focus on patient-orientated outcome measures such as exacerbation rate, with additional tests of small airway function., Trial Registration Number: NCT01171365. Protocol available at http://www.clinicaltrials.gov., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Inhaled corticosteroids (ICSs) are widely used in asthma control. Ciclesonide (CIC) is an ICS with on-site lung activation for potent anti-inflammatory activity., Aims: This study aimed to compare the clinical benefit of CIC with budesonide (BUD) in step-down therapy., Methods: A total of 150 patients with mild-to-moderate asthma well controlled by a combination of ICS and long-acting β2-agonist were randomised to receive either CIC 320 μg (n=75) once daily or 2 inhalations of BUD 200 μg (n=75) twice daily for 12 weeks. The forced expiratory volume in 1s (FEV1), maximum mid-expiratory flow (MMEF) and asthma control test (ACT) scores were measured. Ranked stratification of patients and physicians was assessed., Results: Drug adherence was significantly higher in the CIC group than in the BUD group (76.0% vs. 58.7%, P=0.03). The FEV1 and MMEF remained stable throughout the 12-week CIC treatment. In the BUD group, FEV1 significantly decreased at weeks 4 and 12. MMEF had a higher value in the CIC group than in the BUD group. Both patients and physicians ranked CIC over BUD., Conclusions: CIC is more effective and has better drug adherence than BUD as step-down treatment when asthma is well controlled by combination therapy.

Inhaled corticosteroids such as beclometasone are the drugs of choice for long-term treatment of patients with persistent asthma. There is no tangible difference in efficacy among inhaled corticosteroids, but we have the most experience with beclometasone. Ciclesonide (Alvesco, Nycomed then Takeda), another inhaled cortico-steroid, has been tested in three double-blind trials versus budesonide and six trials versus fluticasone but none versus beclometasone. These trials showed the "non-inferiority" of ciclesonide, mainly in terms of a surrogate endpoint: the change in forced expiratory volume in one second (FEV1) after 12 or 24 weeks of treatment (primary endpoint). However, the doses of ciclesonide used in these trials were higher than the standard doses while doses of the comparator corticosteroids were lower than the standard doses, thus favouring ciclesonide. Local adverse effects of inhaled corticosteroids include oral candidiasis, sore throat and hoarseness. A systematic review conducted by a Cochrane group suggests that ciclesonide does not have a better adverse effect profile than other inhaled corticosteroids used at equivalent doses. Corticosteroid inhalation can also lead to systemic absorption. The practical advantage of once-daily dosing with ciclesonide seems minor. In practice, ciclesonide is neither more effective than the inhaled corticosteroids with which it has been compared, nor does it have fewer adverse effects. It is better to continue to use beclometasone, a drug with which there is more experience.

Introduction: The choice among the different treatments available can have a great impact on the costs of asthma,, Objectives: The objective of this study was to estimate the incremental cost-utility ratio of three inhaled corticosteroids (ICs): budesonide (BUD), fluticasone propionate (FP), and ciclesonide, compared to beclomethasone dipropionate (BDP) (the only IC included in the Compulsory Health Insurance Plan of Colombia),, Methods: A Markov-type model was developed to estimate costs and health outcomes of a simulated cohort of patients less than 18 years of age with persistent asthma treated over a 12-month period. Effectiveness parameters were obtained from a systematic review of the literature. Cost data were obtained from a hospital´s bills and from the national manual of drug prices. The study assumed the perspective of the national healthcare in Colombia. The main outcome was the variable "quality-adjusted life years" (QALY), RESULTS: While treatment with BDP was associated with the lowest cost (£106.16 average cost per patient during 12 months), treatment with FP resulted in the greatest gain in QUALYs (0.9325 QALYs). FP was associated with a greater gain in QALYs compared to BUD and ciclesonide (0.9325 vs. 0.8999 and 0.9051 QALYs, respectively) at lower costs (£231.19 vs. £309.27 and £270.15, respectively), thus leading to dominance. The incremental cost-utility ratio of FP compared to BDP was £19,835.28 per QALY, CONCLUSIONS: BDP is the most cost-effective therapy for treating pediatric patients with persistent asthma when willingness to pay (WTP) is less than £21,129.22/QALY, otherwise, FP is the most cost-effective therapy.

Ciclesonide (CIC) is a novel inhaled corticosteroid (ICS) approved by US Food and Drug Administration for the treatment of persistent asthma, available as a pressurized metered-dose inhaler in two strengths, 80 mcg/activation and 160 mcg/activation. Ciclesonide is a corticosteroid with unique pharmacological profile including a high degree of serum protein binding, a low oral bioavailability and rapid systemic elimination. Ciclesonide is a prodrug metabolized by esterases to desisobutyryl ciclesonide (des-CIC), an active metabolite with a 100-fold greater affinity for the glucocorticoid receptor. It has shown to improve pulmonary functions, reduce the need for oral corticosteroids (OCSs) and cause lesser suppression of the hypothalamic-pituitary-adrenal axis in asthmatic patients. Clinical efficacy studies suggest that Ciclesonide is superior to placebo and is at least as effective as several active comparators with an improved therapeutic margin thereby improving the therapeutic outcome in patients of asthma.

Background: We compared titrating inhaled corticosteroid (ICS) against mannitol airway hyperresponsiveness (AHR) or a reference strategy (control) based on symptoms, reliever use, and lung function in primary care., Methods: One hundred sixty-four patients with persistent asthma were randomized in parallel group fashion following an initial ICS tapering. Subsequent ICS doses (as ciclesonide) were titrated against either the provocative dose of mannitol causing a 10% fall in FEV(1) (PD(10)) (AHR strategy) or a control group (reference strategy) over a 1-year period., Results: One hundred nineteen participants (n = 61 AHR, n = 58 control) completed the study. Time to first mild exacerbation was not significantly different: hazard ratio, 1.29; 95% CI, 0.716-2.31; P = .40. Although there were 27% fewer total number of mild exacerbations over 12 months in AHR vs control groups (n = 84 vs n = 115, P = .03), there was no difference in severe exacerbations (n = 12 vs n = 13). No other significant differences were seen between groups with the exception of mannitol PD(10) and ICS dose. There was a 1.52 (95% CI, 0.61-2.42; P = .001) doubling dose difference in mannitol PD(10) between AHR vs control groups. The final mean daily ciclesonide dose was higher (P < .0001) in AHR vs control groups (514 μg vs 208 μg), with no associated significant suppression of overnight urinary cortisol/creatinine. Significant improvements were seen within the AHR group but not the control group for the provocative concentration of methacholine causing a 20% fall in FEV(1) (P < .05), salivary eosinophilic cationic protein (P < .05), exhaled nitric oxide (P < .05), symptoms (P < .005), and reliever use (P < .001)., Conclusions: Mannitol challenge was well tolerated in a primary care setting. Using mannitol resulted in exposure to a higher dose of ciclesonide, which was associated with equivocal effects on exacerbations without associated adrenal suppression. Large-scale trials using mannitol in patients with more severe disease may now be warranted to further define its role., Trial Registration: ClinicalTrials.gov; No.: NCT01216579; URL: www.clinicaltrials.gov.

Recommended treatment for moderate to severe asthma is the combination of an inhaled corticosteroid and a long-acting beta2-agonist. The present study was designed to evaluate the efficacy of a newly developed fixed combination of ciclesonide and formoterol in comparison to the marketed fixed combination of fluticasone and salmeterol in patients with moderate asthma. This was a phase II, multi-centre, randomized, parallel-group, double-blind, double-dummy study. After a 2-week run-in period, 160 patients with moderate asthma were randomized to a 6-week treatment with ciclesonide/formoterol 320/9 μg bid (CIC/F) or fluticasone propionate/salmeterol 250/50 μg bid (FP/S), both delivered as powder formulations. The primary outcome FEV1 increased during treatment by 0.356 L in the CIC/F group and by 0.288 L in the FP/S group (p < 0.0001). The increases were statistically significant and clinically relevant. The between-treatment analysis demonstrated non-inferiority of CIC/F to FP/S treatment (p < 0.0001). A significant improvement from baseline in lung function, symptom score and rescue medication use was observed in both groups at all time points. No differences were observed between treatments in the frequency of adverse events and overnight urinary cortisol/creatinine ratio. The studied fixed combination of ciclesonide/formoterol is not inferior to the marketed fixed combination of fluticasone/salmeterol in terms of efficacy and tolerability., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Few large-scale studies have examined inhaled corticosteroid treatment in preschool children with recurrent wheeze. We assessed the effects of ciclesonide in preschool children with recurrent wheeze., Methods: We included children 2-6 yrs with recurrent wheeze and a positive asthma predictive index or aeroallergen sensitization to, excluding patients with episodic viral wheezing. After a 2-4-week baseline period, patients with ongoing symptoms or rescue medication use were randomised to once-daily ciclesonide 40, 80, 160 μg or placebo for 24 weeks., Results: The number of wheeze exacerbations requiring systemic corticosteroids was unexpectedly low in all groups: 25 (10.2%) in placebo group, as compared to 11 (4.4%), 18 (7.3%), and 17 (6.7%) in ciclesonide 40, 80, and 160 μg, respectively. The difference in time to first exacerbation was not significantly different between groups (p = 0.786), but the difference in exacerbation rates between placebo and the pooled ciclesonide groups was (p = 0.03). Large and significant (p < 0.0001) improvements in symptom scores and rescue medication use occurred in all groups, including placebo. Improvements in FEV(1) and FEF(25-75) (measured in 284 4-6 yr olds) were larger in the ciclesonide than in the placebo group. No differences in safety parameters (adverse events, height growth, serum and urinary cortisol levels) between ciclesonide and placebo were observed., Conclusions: In preschool children with recurrent wheeze and a positive asthma predictive index, ciclesonide modestly reduces wheeze exacerbation rates and improves lung function. A large placebo response and unexpected selection of patients with mild disease may have affected outcomes, highlighting the heterogeneity of preschool wheezing disorders., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Despite the fact that bronchioles are involved in asthma, there have been limited asthmatic cases showing marked centrilobular opacities on computed tomography (CT) chest scans. Systemic corticosteroids have been administered in such cases, but the efficacy of extra-fine particle inhaled corticosteroids has not been assessed., Case Summary: A previously healthy 64-year-old man presented with a four-month history of productive cough and progressive dyspnea despite a combination therapy with inhaled salmeterol (50 μg bid) and fluticasone (500 μg bid), sustained-release theophylline, and pranlukast because of suspicion of asthma. Physical examination revealed wheezing at the end of forced expiration. High resolution CT chest scan showed diffuse centrilobular opacities, bronchiectatic changes, and bronchial wall thickening. Transbronchial lung biopsy, bronchoalveolar lavage fluid, and transbronchial biopsy all showed predominant eosinophil infiltrates, suggesting that eosinophilic inflammation across the entire airway tree caused the abnormal CT findings. Alveolar fraction of exhaled nitric oxide level, a non-invasive marker of eosinophilic peripheral airway inflammation, was also elevated. Because he refused systemic corticosteroids, inhaled ciclesonide (400 μg bid) and inhaled tiotropium were added on to his current medication under careful observation. His symptoms, pulmonary function and CT findings promptly improved, and he had fully recovered at follow-up., Discussion: Extra-fine particle inhaled corticosteroids could be an alternative approach in centrilobular opacities caused by eosinophilic peripheral airway inflammation.

Purpose of Review: 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., Recent Findings: 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., Summary: 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.

Objective: To investigate the efficacy and safety of ciclesonide in patients with severe asthma over a 1-year period., Research Design and Methods: Patients aged 18 - 75 years with persistent asthma were enrolled in a 12-week, double-blind, randomized study and treated with ciclesonide 320 or 640 μg twice daily (b.i.d.) with the option of continuing in a 40-week extension phase (EP)., Main Outcomes Measures: Change in morning peak expiratory flow (PEF) from baseline to 12 weeks and safety over 1 year., Results: 365 patients were randomized and 275 continued into the EP. During 12 weeks' treatment, morning peak expiratory flow significantly increased by 16 l/min (p < 0.001) and 14 l/min (p = 0.001) in the 320 and 640 μg b.i.d. groups, respectively. Both doses significantly reduced total asthma symptom scores by 0.29 (p < 0.0001). In both groups, the incidence of adverse effects (AEs) was low and mean cortisol levels in serum and urine were not suppressed during the EP., Conclusions: Ciclesonide 320 μg b.i.d. sustained lung function and asthma symptoms in patients with severe asthma over 12 weeks' treatment, and maintained lung function during a 40-week EP; ciclesonide 640 μg b.i.d. did not provide additional benefits. Long-term use of ciclesonide was not associated with increased local AEs or negative effects on cortisol levels.

Objective: To evaluate the efficacy and safety of three doses of ciclesonide (with or without spacer) in children with persistent asthma., Patients and Methods: This was a multicentre, double-blind, placebo-controlled, 12-week study of ciclesonide 40, 80 or 160 μg (once daily pm). Children (6-11 years) were randomised 1:1 to treatment via a metered dose inhaler (MDI) or MDI plus spacer. The primary variable was change from baseline in mean morning peak expiratory flow (PEF). Secondary variables included: time to first lack of efficacy (LOE), asthma control, forced expiratory volume in 1 s (FEV(1)), asthma symptom score and quality of life (QoL). Safety assessments included: adverse events (AEs), urinary cortisol excretion and body height., Results: In total, 1073 children received treatment. At endpoint, mean morning PEF significantly improved with all doses of ciclesonide vs. placebo. There was no difference over placebo in time to first LOE, but ciclesonide was superior to placebo on asthma control, symptom score, FEV(1) and QoL. There were no differences between the spacer or non-spacer subgroups. The incidences of AEs were comparable between treatment groups (approximately 35%) and there were no between-group differences in body height or urinary cortisol., Conclusions: Ciclesonide 40-160 μg once daily is effective and well tolerated in children with persistent asthma; its efficacy and safety are unaffected by the use of a spacer. clinicaltrials.gov registration number: NCT00384189., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Inhaled corticosteroids, such as fluticasone propionate (FP) and ciclesonide (CIC), are commonly used for the treatment of asthma. The objectives of this study were to characterize pharmacokinetics (PK) and pharmacodynamics (PD) of FP and a pharmacologically active metabolite of CIC (desisobutyryl-ciclesonide [Des-CIC]) using a nonlinear mixed-effects modeling approach, to investigate selected covariate effects on PK and PD parameters of FP and Des-CIC, and to assess the systemic effects of FP and CIC on serum cortisol suppression in patients with persistent asthma. This was a randomized, double-blind, placebo-controlled, double-dummy, 5-period, crossover, multicenter clinical study. A total of 32 patients were enrolled and given basic asthma medication (salmeterol 50 µg twice per day [BID] and CIC 160 µg daily in the evening) through the entire study. During crossover periods, patients were given placebo or CIC 160 µg BID (ex actuator), CIC 320 µg BID (ex actuator), FP 220 µg BID (ex actuator), or FP 440 µg BID (ex actuator). The FP and Des-CIC PK were described using a 1-compartment and a 2-compartment linear model with first-order absorption process. The FP population PK parameter estimates of the first-order rate constant, relative clearance, and volume of distribution were 4.07 1/h, 890 L/h, and 9800 L, respectively. The Des-CIC PK parameter estimates of the first-order absorption rate constant were 2.63 1/h, clearance 202 L/h (non-CIC treatment) or 271 L/h (CIC treatment), and volume of distribution 947 L. Gender was a significant covariate on the maximum cortisol release rate (male, 3440 µg/h; female, 4310 µg/h). The CIC showed the least serum cortisol suppression of the tested dosing regimens.

Objective: Strongyloides stercoralis is a soil-transmitted intestinal nematode that has been estimated to infect at least 60 million people, especially in tropical and subtropical regions. Strongyloides infection has been described in immunosupressed patients with lymphoma, rheumatoid arthritis, diabetes mellitus etc. Our case who has rheumatoid arthritis (RA) and bronchial asthma was treated with low dose steroids and methotrexate., Methods: A 68 year old woman has bronchial asthma for 55 years and also diagnosed RA 7 years ago. She received immunusupressive agents including methotrexate and steroids. On admission at hospital, she was on deflazacort 5 mg/day and methotrexate 15 mg/week. On her physical examination, she was afebrile, had rhonchi and mild epigastric tenderness. She had joint deformities at metacarpophalengeal joints and phalanges but no active arthritis finding., Results: Oesophagogastroduodenoscopy was performed and it showed hemorrhagic focus at bulbus. Gastric biopsy obtained and showed evidence of S.Stercoralis infection. Stool and sputum parasitological examinations were also all positive for S.stercoralis larvae. Chest radiography result had no pathologic finding. Albendazole 400 mg/day was started for 23 days. After the ivermectin was retrieved, patient was treated with oral ivermectin 200 μg once a day for 3 days. On her outpatient control at 15th day, stool and sputum samples were all negative for parasites., Conclusion: S.stercoralis may cause mortal diseases in patients. Immunosupression frequently causes disseminated infections. Many infected patients are completely asymptomatic. Although it is important to detect latent S. stercoralis infections before administering chemotherapy or before the onset of immunosuppression in patients at risk, a specific and sensitive diagnostic test is lacking. In immunosupressed patients, to detect S.stercoralis might help to have the patient survived and constitute the exact therapy.

Background: Adrenal suppression secondary to high-dose inhaled corticosteroid use has been reported in children., Methods: The authors report the use of ciclesonide to reverse adrenal suppression secondary to inhaled fluticasone use in four pediatric patients., Results: In these four children, hypothalamic-pituitary-adrenal axis function normalized after the patients were changed to ciclesonide, while good asthma control was maintained., Conclusions: Ciclesonide should be considered for the reversal of adrenal suppression secondary to the use of fluticasone, and perhaps other older inhaled corticosteroids as well.

Importance of the Field: Asthma is a chronic disease characterized by airway inflammation and hyper-responsiveness. Inhaled corticosteroids (ICSs) constitute the guideline-recommended first-line therapy for persistent asthma. However, concerns regarding ICS-related adverse events may contribute to their underutilization by physicians and patients., Areas Covered in This Review: The currently available published data on the pharmacokinetic and pharmacodynamic properties, safety and efficacy of the ICS, ciclesonide, is described. Peer-reviewed publications (1996 - 2009) on the pharmacodynamic and pharmacokinetic profile, safety and efficacy of ciclesonide were reviewed., What the Reader Will Gain: Ciclesonide is delivered as an inactive prodrug, which is cleaved to the active molecule by intracellular esterases located in the lungs. This and other pharmacodynamic and pharmacokinetic properties may limit the amount of active molecule outside the lung and may reduce the incidence of side effects. Randomized placebo-controlled studies found that ciclesonide can initiate and maintain disease control in subjects with persistent asthma of all disease severities. Moreover, studies have found that ciclesonide is as effective as other ICSs in establishing and controlling disease symptoms. Controlled clinical trials also showed that ciclesonide is associated with minimal systemic and local treatment-related adverse events., Take Home Message: Published findings indicate that ciclesonide is effective at initiating and maintaining asthma control and is well tolerated, with a positive safety profile.

Background: Although it is well established that the incidence of bronchial asthma is higher in the athlete population than in the general population, little information exists about the efficacy of treatment of bronchial asthma in the athlete population., Objectives: We conducted this study with the objective of determining the efficacy of treatment of bronchial asthma in an athlete population living in Niigata Prefecture, Japan., Methods: We conducted a retrospective study of bronchial asthma in an athlete population. Athletes diagnosed as having asthma, based on the Global Initiatives for Asthma (GINA) guidelines, who visited the Niigata Institute for Health and Sports Medicine between January 2007 and June 2008 were enrolled in this study. We compared two groups of patients, a group treated with ciclesonide (CIC) alone and another treated with montelukast alone, with the treatment duration lasting at least 3 months in both groups. The CIC or montelukast groups were compared in terms of the clinical symptoms, pulmonary function parameters, and fraction of exhaled nitric oxide (FENO)., Results: There were no significant differences in the sex distribution, age, frequency of symptoms, pulmonary function parameters, or other examination data before treatment between the CIC and montelukast groups. The CIC group tended to show better symptom control and to need fewer changes of treatment than the montelukast group. While improvements of the pulmonary function parameters and FENO values were observed in the CIC group, no significant changes of these parameters were observed in the montelukast group., Conclusions: These data suggest that CIC offers greater promise for the control of asthma than montelukast in the athlete population, although further investigation is required.

Rationale: Oral corticosteroids effectively treat asthma exacerbations but are associated with well-described side effects., Objective: This study compared the efficacy and safety of a high dose of an inhaled corticosteroid with oral prednisolone in patients with worsening of their asthma after medication withdrawal., Methods: Patients tapered off their inhaled corticosteroids until they reached predefined criteria of "worsening asthma". Randomized patients (n=130) were treated double blind with either ciclesonide 800mug twice daily (starting with 800mug hourly for 3h after randomization) or prednisolone 40mg once daily for 2 weeks. Spirometry, daily asthma symptoms, morning and evening peak expiratory flow and blood parameters were assessed in all, methacholine challenge and inflammatory measures were determined in induced sputum in a subset of patients., Results: Ciclesonide was as effective as prednisolone in improving forced expiratory flow in 1s, morning peak expiratory flow and symptoms, the latter improving more rapidly with ciclesonide. No differences were found in methacholine responsiveness or inflammatory measures in sputum or blood. Ciclesonide caused significantly less reduction in morning plasma cortisol levels (p<0.0001)., Conclusion: This study shows that inhaled ciclesonide (800mug twice daily) has comparable efficacy to oral prednisolone (40mg once daily) to regain asthma control in patients with asthma worsening. The more rapid onset and smaller effect on cortisol suppression suggest a better safety profile of ciclesonide.

We compared the systemic and clinical effects of ciclesonide (CIC) and fluticasone propionate (FP) administered, in addition to CIC 160 microg x day(-1) and salmeterol 50 microg twice daily, in 32 patients with persistent asthma using a randomised double-blind, placebo-controlled, double-dummy, five-period crossover design. All patients exhibited a provocative concentration leading to a 20% decrease in forced expiratory volume in 1 s (PC(20)) methacholine <8 mg x mL(-1) and a PC(20) adenosine <60 mg x mL(-1). Primary outcome was 24-h serum cortisol suppression after 7 days. Secondary outcomes were changes in PC(20) methacholine and adenosine after 9 days. FP 500 microg x day(-1) and 1,000 microg x day(-1) significantly suppressed cortisol secretion versus placebo by -46.2 (95% confidence interval (CI) -83.8- -8.5) nmol x L(-1) and by -76.1 (95% CI -112.9- -39.3) nmol x L(-1), respectively. Neither dose of CIC (320 nor 640 microg x day(-1)) had a significant suppressive effect (-28.2 (95% CI -65.5-9.2) nmol x L(-1) and -37.3 (95% CI -74.7-0.0) nmol x L(-1), respectively). Differences between FP 1,000 microg x day(-1) and both CIC treatments were statistically significant (CIC 320 microg x day(-1): -48.0 (95% CI -84.8- -11.1) nmol x L(-1); CIC 640 microg x day(-1): -38.8 (95% CI -75.7- -1.9) nmol x L(-1)). Compared with placebo, the increase in PC(20) adenosine after the four treatments was small, but significant. Greater improvements in PC(20) adenosine were seen with FP 500 microg x day(-1) (1.8 (95% CI 1.0-2.6) doubling concentrations) compared with CIC 320 microg x day(-1) (0.9 (95% CI 0.1-1.7) doubling concentrations). No significant difference was seen between CIC 640 microg x day(-1) and FP 1,000 microg x day(-1). For a similar decrease in hyperresponsiveness, cortisol secretion was suppressed significantly with moderate-to-high doses of fluticasone propionate, but not with ciclesonide.

Background: Ciclesonide is a new inhaled corticosteroid (ICS). Information about its clinical efficacy and safety in relation to other ICS in children is needed for clinical positioning., Objective: This 12-week, randomized, double-blind, double-dummy, three-arm, parallel-group study compared the efficacy and safety of ciclesonide with fluticasone propionate in children with mainly moderate and severe persistent asthma., Methods: Seven hundred and forty-four patients (aged 6-11 years) were randomized to ciclesonide (80 or 160 microg once daily) or fluticasone propionate (88 microg twice daily), following a 2-4-week run-in. Efficacy measurements included forced expiratory flow in 1s (FEV(1)), morning peak expiratory flow (PEF), asthma symptom scores, rescue medication use and quality of life. Systemic effect was assessed by 24-hour urine free cortisol adjusted for creatinine., Results: FEV(1) and morning PEF increased from baseline in all groups (p<0.0001). Ciclesonide 160 microg was not inferior to fluticasone propionate 176 microg for FEV(1) (p=0.0030, one-sided). In all groups, asthma symptom score sums and rescue medication use significantly improved (p<0.0001). The percentages of asthma symptom-, rescue medication- and nocturnal awakening-free days were high, with no significant differences between treatments. Quality of life scores improved with all treatments (p<0.0001). A significant dose-response occurred between low and higher doses of ciclesonide for exacerbations and asthma control definitions. The incidences of adverse events were comparable across treatments. Urine free cortisol levels decreased significantly with fluticasone propionate (p=0.0103), but not with ciclesonide., Conclusion: Once-daily ciclesonide has a clinical effect similar to that of fluticasone propionate, but does not suppress cortisol excretion, in children with moderate and severe asthma.

Inhaled corticosteroids (ICSs) are considered the most effective therapy currently available for persistent asthma and is the guideline-recommended first-line treatment for all patients requiring controller medication; however, the potential for oropharyngeal and systemic adverse events can be a barrier to their use. Ciclesonide (CIC) is a new ICS with a unique pharmacologic profile that may confer a favorable safety profile. This study was designed to provide a comprehensive review of currently available safety data for CIC in adults and children with asthma of all severities. The literature was reviewed for all clinical trials with CIC reporting safety results (no date restrictions; English language only). Clinical trials with CIC in children and adults showed a very low occurrence of oropharyngeal adverse events (including oral candidiasis, pharyngitis, and hoarseness) and minimal systemic activity. In particular, no clinically relevant effect on cortisol levels was observed, compared with placebo or active comparators, even with high-dose CIC treatment (up to 1280 microg/day) and in asthma of all severities. Furthermore, there was no clinically relevant effect of CIC treatment on growth in children with mild asthma compared with placebo. The favorable safety profile of CIC may allay patient and physician concern regarding ICS when using this agent. Guideline-recommended use of ICS medications may help optimize treatment outcomes in asthma.

Inhaled corticosteroids (ICSs) are a first-line treatment for persistent asthma. This study was designed to compare the efficacy and safety of ciclesonide (CIC) in subjects with mild-to-moderate persistent asthma not using an ICS. This was a multicenter, double-blind, parallel-group, placebo-controlled, 16-week study in subjects who were > or =12 years old, had a > or =6-month history of persistent asthma, a forced expiratory volume in 1 second (FEV(1)) of > or =60 to < or =85% predicted, and who were not using an ICS < or =30 days before study entry. Subjects were randomized to CIC, 80 microg twice daily (CIC80 b.i.d.; n = 170); CIC, 160 microg once daily in the morning (CIC160 q.d. in the A.M.; n = 173); CIC80 b.i.d. for 4 weeks followed by CIC160 q.d. for 12 weeks (CIC80 b.i.d./CIC160 q.d.; n = 171); or placebo (n = 177). Change in FEV(1) from baseline to the average of weeks 12 and 16 (primary end point) and to week 16, A.M. peak expiratory flow, rescue albuterol use, nighttime awakenings, asthma symptom scores, and safety were evaluated. FEV(1) improved from baseline to the average of weeks 12 and 16 for CIC80 b.i.d. (+0.30L; p < 0.0001), CIC160q.d. (+0.19L; p < 0.0001), CIC80 b.i.d./CIC160 q.d. (+0.19L; p < 0.0001), and placebo (+0.06L; p = 0.0251); improvement was greatest for CIC80 b.i.d. (p < 0.01). At week 16, all CIC treatments significantly improved FEV(1) and A.M. PEF from baseline (p < 0.0001) and compared with placebo (p < or = 0.015). All treatments reduced albuterol use and nighttime awakenings and improved asthma symptom scores (p < or = 0.05 versus baseline); these improvements were greater for CIC80 b.i.d. than for placebo (p < 0.01). The incidence of adverse events was similar among treatment groups (range, 53-58%). In this study, CIC80 b.i.d. improved disease control in subjects with mild-to-moderate persistent asthma not using an ICS and provided greater improvements than CIC160 q.d.

Inhaled corticosteroids (ICSs) are recommended as first-line treatment for persistent asthma. This study was designed to evaluate the ability of ciclesonide (CIC) in subjects with stable asthma previously receiving another ICS or ICS/long-acting beta(2)-agonist (LABA) to maintain asthma disease control. In this 12-week, multicenter, double-blind, parallel-group study, subjects aged > or =12 years with stable mild-to-moderate persistent asthma were switched at randomization from an ICS or ICS/LABA to CIC, 80 microg twice daily (CIC80 b.i.d.; n = 149); CIC, 160 microg once daily (CIC160 q.d.; n = 150); or placebo (n = 147). Change in forced expiratory volume in 1 second (FEV(1); primary end point), morning peak expiratory flow (PEF), rescue albuterol use, total asthma symptom score, nighttime awakenings, and safety were evaluated. FEV(1) improved from baseline to week 12 after CIC80 b.i.d. treatment (+0.07 L; p = 0.0232), and was maintained after CIC160 q.d. (+0.01 L; p = 0.6217). FEV(1) declined from baseline after placebo (-0.12 L; p < 0.0001) and significantly versus CIC treatments (p < 0.001). At week 12, morning PEF maintained baseline values after CIC80 b.i.d. (-4.43 L/minute; p = 0.1272) and decreased after CIC160 q.d. (-5.77 L/minute; p = 0.0490) and placebo (-12.82 L/minute; p < 0.0001); the difference between CIC80 b.i.d. and placebo was significant (p = 0.035). Baseline albuterol use, total daily asthma score, and nighttime awakenings were maintained after CIC treatments (p > 0.25), but increased after placebo (p < or = 0.002); the difference between CIC80 b.i.d. and placebo was significant (p < 0.02). Incidence of adverse events was similar among treatment groups (range, 52.0-57.9%). In this study, CIC80 b.i.d. maintained asthma control in subjects with stable mild-to-moderate asthma previously treated with ICS or ICS/LABA, was well tolerated, and, in general, was better than CIC160 q.d. in maintaining disease control.

Background: In asthma small airways inflammation often persists despite inhaled corticosteroids therapy., Objective: To discuss the effects of ciclesonide, a newer inhaled corticosteroid on small airways inflammation and the reliability of some biomarkers of small airways inflammation in asthma., Methods and Results: Evaluation of a study assessing the short-term effects of ciclesonide on small airways inflammation in patients with mild to moderate asthma., Conclusions: Ciclesonide could have beneficial effects on small airways inflammation and some of the outcome measures used as efficacy endpoints could represent possible biomarkers of small airways involvement in obstructive chronic respiratory diseases.

Objective: To review the basis for the estimated comparative daily dosages of inhaled corticosteroids for children and adults that are presented in the National Heart, Lung, and Blood Institute's Expert Panel Report 3; in addition, the pharmacodynamic and pharmacokinetic basis for potential clinical differences among inhaled corticosteroids is discussed., Data Sources: A complete MEDLINE search was conducted of human studies of asthma pharmacotherapy published between January 1, 2001, and March 15, 2006, followed by a PubMed search up until August 2008, using ciclesonide, inhaled corticosteroids, and pharmacokinetics as key words. Product information on each inhaled corticosteroid was also included., Study Selection and Data Extraction: Comparative clinical trials of inhaled corticosteroids and systematic reviews for efficacy comparisons were evaluated. Extensive literature reviews, meta-analyses, and selected clinical studies that illustrate or represent specific points of view were selected. Pharmacodynamic and pharmacokinetic data extracted from previously published reviews and specific studies were included., Data Synthesis: Pharmacodynamic characteristics (glucocorticoid receptor binding) and lung delivery determine the relative clinical efficacy and pharmacokinetic properties (oral bioavailability, lung retention, systemic clearance) and determine comparative therapeutic index of the inhaled corticosteroids. Secondary pharmacokinetic differences (intracellular fatty acid esterification, high serum protein binding) that have been posited to improve duration of action and/or therapeutic index are unproven, and current comparative clinical trials do not support the hypotheses that they provide an advantage. Ultrafine particle meter-dose inhalers (MDIs) have not demonstrated superior asthma control or improved safety over older MDIs. All of the inhaled corticosteroids demonstrate efficacy with once-daily dosing, and all are more effective when dosed twice daily., Conclusions: Current evidence suggests that all of the inhaled corticosteroids have sufficient therapeutic indexes to provide similar efficacy and safety in low to medium doses. Whether or not some of the newer inhaled corticosteroids offer any advantages at higher doses has yet to be determined.

Health-related quality of life (HRQOL) provides information on patients' everyday physical, emotional, and social difficulties that traditional measurements of asthma severity (pulmonary function assessments and asthma symptom scores) may not reflect. Our objective is to evaluate the effect of ciclesonide (CIC) on HRQOL in a combined analysis of two identical, 12-week, multicenter, double-blind, parallel-group, placebo-controlled trials. Patients (N=1015) with mild-to-moderate asthma (aged >or=12 years; forced expiratory volume in 1 s 60-85% predicted at randomization after administration of single-blind placebo during baseline [5-28 days]) were randomized to receive placebo or CIC 80, 160, or 320 microg (ex-actuator) once daily. HRQOL was assessed using the Juniper Asthma Quality-of-Life Questionnaire (AQLQ). The overall AQLQ score and individual domain scores (activity limitation, symptoms, emotional function, and exposure to environmental stimuli) were recorded at baseline, week 4 and week 12. Statistically significant improvements (p<0.0001) in overall AQLQ scores were observed for all CIC groups versus placebo (CIC80, 0.50; CIC160, 0.61; CIC320, 0.69; placebo, 0.14) from baseline to week 12. Similar significant improvements were observed for all CIC groups in the four individual domain scores, except the CIC80 environmental stimuli domain score. A greater proportion of CIC-treated patients achieved a minimally important difference in overall AQLQ score (>or=0.5 improvement) by week 4, which was sustained through to week 12, compared with placebo (week 12: CIC80, 47.1%; CIC160, 50%; CIC320, 50.6%; placebo, 31%). In this combined analysis, once-daily CIC significantly improved HRQOL compared with placebo, in adults/adolescents with mild-to-moderate persistent asthma.

Background: Inhaled corticosteroids (ICS) are an integral part of asthma management, and act as an anti-inflammatory agent in the airways of the lung. These agents confer both significant benefit in terms of symptom management and improvement in lung function, but may also cause harm in terms of local and systemic side-effects. Ciclesonide is a novel steroid that is metabolised to its active component in the lung, making it a potentially useful for reducing local side effects., Objectives: To assess the efficacy and adverse effects of ciclesonide relative to those of other inhaled corticosteroids in the management of chronic asthma., Search Strategy: We searched the Cochrane Airways Group register of trials with pre-defined terms. Additional searches of PubMed and Clinicalstudyresults.org were undertaken. The literature searches for this review are current up to June 2007., Selection Criteria: Randomised parallel or crossover studies were eligible for the review. We included studies comparing ciclesonide with other steroids both at nominally equivalent dose or lower doses of ciclesonide., Data Collection and Analysis: Two review authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials., Main Results: Twenty one trials involving 7243 participants were included. Equal daily doses of ciclesonide and beclomethasone (BDP) or budesonide (BUD) gave similar results for peak expiratory flow rates (PEF), although forced vital capacity (FVC) was higher with ciclesonide. Data on forced expired volume in one second (FEV1) were inconsistent. Withdrawal data and symptoms were similar between treatments. Compared with the same dose of fluticasone (FP), data on lung function parameters (FEV1, FVC and PEF) did not differ significantly. Paediatric quality of life score favoured ciclesonide. Candidiasis was less frequent with ciclesonide, although other side-effect outcomes did not give significant differences in favour of either treatment. When lower doses of ciclesonide were compared to BDP or BUD, the difference in FEV1 did not reach significance but we cannot exclude a significant effect in favour of BDP/BUD. Other lung function outcomes did not give significant differences between treatments. Paediatric quality of life scores did not differ between treatments. Adverse events occurred with similar frequency between ciclesonide and BDP/BUD. Comparison with FP at half the nominal dose was undertaken in three studies, which indicated that FEV1 was not significantly different, but was not equivalent between the treatments (per protocol: -0.05 L 95% confidence intervals -0.11 to 0.01)., Authors' Conclusions: The results of this review give some support to ciclesonide as an equivalent therapy to other ICS at similar nominal doses. The studies assessed low doses of steroids, in patients whose asthma required treatment with low doses of steroids. At half the dose of FP and BDP/BUD, the effects of ciclesonide were more inconsistent The effect on candidiasis may be of importance to people who find this to be problematic. The role of ciclesonide in the management of asthma requires further study, especially in paediatric patients. Further assessment against FP at a dose ratio of 1:2 is a priority.

Background: Inhaled corticosteroids are an integral part of asthma management, and act as an anti-inflammatory agent in the airways of the lung. These agents confer significant benefit in terms of symptom management and improvement in lung function, but may also cause harm in terms of local and systemic side-effects. Ciclesonide is a novel steroid that has efficient distribution and release properties that mean it can be taken once daily, making it potentially useful in ongoing asthma management., Objectives: To assess the efficacy of inhaled ciclesonide in adults and children with chronic asthma., Search Strategy: We searched the Cochrane Airways Group register of trials with pre-defined terms. Additional searches of CENTRAL and PubMed were undertaken. The literature searches for this review are current up to June 2007., Selection Criteria: Randomised parallel or crossover studies were eligible for the review. We included studies comparing ciclesonide with placebo, and we also included studies comparing ciclesonide at different doses., Data Collection and Analysis: Two authors assessed studies for inclusion in the review, extracted data independently and checked each others' work. We contacted study investigators in order to obtain additional data. Extracted data were entered into RevMan 4.2 and analysed as fixed effect mean differences for continuous data, and fixed effect risk ratios for dichotomous data., Main Results: Eighteen trials (reporting 20 study comparisons) met the review entry criteria. We report findings from 18 group comparisons where data were available (6343 participants, of whom 1692 were children). Ciclesonide versus placebo: The short duration of the included studies means that there is a lack of data with respect to the impact of ciclesonide on asthma exacerbations. At doses of 100 mcg/d or less up to 400 mcg/d in mild to moderate asthma, ciclesonide improved lung function, asthma symptoms and rescue inhaler use, compared with placebo.Dose response outcomes: Comparisons of 100 versus 200 mcg/d, 100 versus 400 mcg/d and 400 versus 800 mcg/d did not yield significant differences in lung function outcomes. Adverse event data were not available in sufficient detail to permit assessment of the safety profile of this drug., Authors' Conclusions: Ciclesonide was more effective than placebo, in the short term, in improving lung function in patients with mild to moderate asthma previously treated with inhaled corticosteroids. There remain questions as to dose response, and the lack of data on the longer term impact on exacerbations and safety profile should be addressed in future studies.

Background: The relationship between eosinophilic airway inflammation and exercise-induced bronchoconstriction (EIB), and the response to inhaled corticosteroid (ICS) therapy was examined., Methods: Twenty-six steroid-naïve asthmatic patients with EIB were randomized to two parallel, double-blind, crossover study arms (13 subjects in each arm). Each arm compared two dose levels of inhaled ciclesonide that were administered for 3 weeks with a washout period of 3 to 8 weeks, as follows: (1) 40 vs 160 microg daily; and (2) 80 vs 320 microg daily. Baseline and weekly assessments with exercise challenge and sputum analysis were performed., Results: Data were pooled and demonstrated that 10 subjects had baseline sputum eosinophilia >or= 5%. Only high-dose ICS therapy (ie, 160 and 320 microg) significantly attenuated the sputum eosinophil percentage. Sputum eosinophil percentage significantly correlated with EIB severity, and predicted the magnitude and temporal response of EIB to high-dose therapy, but not to low-dose therapy (ie, 40 and 80 microg). Low-dose ICS therapy provided a significant reduction in EIB at 1 week, with little additional improvement thereafter, irrespective of baseline sputum eosinophil counts. In contrast, high-dose ICS therapy provided a significantly greater improvement in EIB in subjects with sputum eosinophilia compared to those with an eosinophil count of < 5%. The difference between the eosinophilic groups in the magnitude of improvement in EIB was evident after the first week of high-dose ICS therapy and increased with time., Conclusions: These results suggest that eosinophilic airway inflammation may be important in modifying the severity of EIB and the response to ICS therapy. Measurements of sputum eosinophil percentage may, therefore, be useful in predicting the magnitude and temporal response of EIB to different dose levels of ICSs., Trial Registration: clinicaltrial.gov; Identifier: NCT00525772.

Objective: Demonstrating clinical benefit of higher doses of inhaled corticosteroids in asthma is frequently problematic owing to their relatively flat dose-response curve in this condition. In this study we compared the efficacy and safety of a fourfold difference in the dose of ciclesonide-ciclesonide 320 microg twice daily (CIC640) versus ciclesonide 160 microg once daily (CIC160)-in patients with severe persistent asthma., Methods: Patients with bronchial asthma (6 months) were included in this randomized, double-blind study. After receiving fluticasone propionate 250 microg twice daily during run-in, patients were randomized to CIC160 (n=339) or CIC640 (n=341) for 12 weeks. Primary endpoints were time to first asthma exacerbation and forced expiratory volume in 1s (FEV(1)). Secondary endpoints included other lung function variables, asthma symptom scores and rescue medication use (RMU)., Results: Asthma exacerbations occurred in 12.7% of patients receiving CIC160 and 6.7% receiving CIC640. CIC640 was superior for time to first exacerbation (p=0.0050, one-sided). FEV(1) increased significantly with CIC160 and CIC640 (least squares mean+/-SE of mean: 269+/-31 and 332+/-31 mL, respectively; p<0.0001), with no significant difference between groups. Change in % predicted FEV(1) and morning peak expiratory flow (PEF) were significantly higher with CIC640 (p<0.05). Asthma symptom score sums and RMU decreased in both groups; CIC640 was statistically superior (p=0.0108 and 0.0005, respectively). No unexpected adverse events were reported in either group and the majority of the events reported were mild or moderate in intensity. No significant changes in serum cortisol were observed from the baseline to the study end. Small decreases in creatinine-adjusted 24h urine cortisol levels from baseline were seen in both the treatment groups, which, due to the large patient numbers, were statistically significant (p<0.05); however, no dose-response effect was seen and the difference between groups was not significant (p=0.7892)., Conclusion: CIC640 was superior to CIC160 for time to first exacerbation, % predicted FEV1, morning PEF, asthma symptom score sum and RMU in patients with severe asthma; both doses had similar tolerability profiles and no significant changes in serum cortisol were seen in either treatment group.

Ciclesonide (Alvesco) is an inhaled corticosteroid used in the preventative treatment of persistent bronchial asthma in adults, adolescents and, in some countries, children. The drug is delivered by a non-chlorofluorocarbon hydrofluoroalkane (HFA) metered-dose inhaler (MDI). In the lungs, ciclesonide is converted to an active metabolite, which is responsible for the beneficial effects of the drug in patients with asthma. Ciclesonide and its active metabolite have low systemic bioavailability and therefore have a low potential to produce systemic adverse events. Inhaled ciclesonide delivered by HFA-MDI is effective in the prophylactic treatment of persistent asthma in adults, adolescents and children, and is generally well tolerated. In general, ciclesonide improves lung function and reduces asthma symptoms and rescue medication use in adults and adolescents with asthma of varying severity. The drug is generally no less effective than other inhaled corticosteroids with regard to maintaining or improving lung function and may have a more favourable tolerability profile than some other agents in this class. Ciclesonide has also shown efficacy in paediatric patients with asthma. Data on its long-term effects on other clinical outcomes, such as asthma exacerbations, would be of interest. Further comparative and long-term studies would also be beneficial in order to definitively position ciclesonide with respect to other inhaled corticosteroids. In the meantime, ciclesonide offers an effective and well tolerated first-line preventative treatment option for persistent asthma.