Fluticasone Propionate Group Research Articles

Inhaled fluticasone propionate is effective as well as oral prednisone in reducing sputum eosinophilia during exacerbations of asthma which do not require hospitalization

The aim of this study was to evaluate whether fluticasone propionate (FP) is effective as well as prednisone (P) in reducing sputum eosinophilia and in improving airway obstruction due to asthma exacerbations not requiring hospitalization. We measured, in a parallel-group, double-blind double-dummy, randomized study, sputum and blood inflammatory cell counts and soluble mediators in 37 asthmatic subjects during a spontaneous exacerbation of asthma (Visit 1) and after a 2 week (Visit 2) treatment with inhaled FP (1000 μg bid) (Group A, n = 18 ) or a reducing course of oral P (Group B, n = 19 ). Asthma exacerbation was accompanied by sputum eosinophilia (eosinophils >2%) in almost all patients (95%). FP improved FEV 1 (from 53.9%±16.8 at Visit 1 to 76.4%±21.2 at Visit 2, p = 0.0001 ) and reduced the percentage of sputum eosinophils (from 38%[0–78] to 3%[1–31, p = 0.0008 ) as well as oral P (FEV 1: from 51.5%±14.4 to 83.6%±21.1, p = 0.0001 ; sputum eosinophils: from 52%[1–96] to 11%[0–64], p = 0.0003 ). At Visit 2, sputum eosinophils were significantly lower in Group A than in Group B. P but not FP induced significant decrease in blood and sputum ECP. Oxygen saturation, PEF variability, symptom score and use of rescue medication similarly improved in both groups. We conclude that FP is effective at least as well as P in reducing sputum eosinophilia and in improving airway obstruction due to asthma exacerbation. However, the cost/effectiveness ratio of this option should be further evaluated.

Effect of fluticasone propionate–salmeterol therapy on seasonal changes in airway responsiveness and exhaled nitric oxide levels in patients with pollen-induced asthma

There has been concern that in allergic asthmatic patients there might be an interactive effect on inflammation between regular salmeterol use and exposure to allergens, resulting in increased airway responsiveness. To determine the effects of salmeterol on allergen-induced changes in airway responsiveness and exhaled nitric oxide (ENO) levels in allergic asthmatic patients concomitantly taking inhaled corticosteroids. Forty-two asthmatic patients sensitized to pollen allergens were randomly allocated to treatment with fluticasone propionate-salmeterol (n=21) or fluticasone propionate alone (n=21). Spirometry, the methacholine provocation concentration causing a 20% decline in forced expiratory volume in 1 second (PC20), the adenosine 5'-monophosphate (AMP) PC20, and ENO levels were measured before and at the height of the pollen season after 6 weeks of treatment. Changes in the methacholine PC20, the AMP PC20, and ENO levels were not significantly different between treatment groups. No significant changes in the AMP PC20 were observed among the fluticasone propionate-salmeterol and fluticasone propionate groups during natural pollen exposure. However, a significant increase in the methacholine PC20 was observed in the fluticasone propionate-salmeterol group (P = .03) and in the fluticasone propionate group (P = .04); ENO concentrations decreased significantly in both groups during natural allergen exposure (P = .009 and .005). In patients with pollen-induced asthma, treatment with either fluticasone propionate or fluticasone propionate-salmeterol is associated with significant reductions in methacholine responsiveness and ENO concentrations, even during natural pollen exposure. Furthermore, at least in patients with mild asthma, natural allergen exposure and the regular use of fluticasone propionate-salmeterol are not associated with a greater increase in ENO levels and airway responsiveness than natural allergen exposure and fluticasone propionate use alone.

Comparative Efficacy and Safety of Low-dose Fluticasone Propionate and Montelukast in Children with Persistent Asthma

To evaluate efficacy, safety, health outcomes, and cost-effectiveness of fluticasone propionate (FP) versus montelukast (MON) in 342 children (6 to 12 years of age) with persistent asthma. Randomized, double-blind, 12-week study of treatment with FP inhalation powder 50 mug twice daily or MON chewable 5 mg once daily for 12 weeks. Compared with MON, FP significantly increased mean percent change from baseline FEV1 (forced expiratory volume in 1 second) (P=.002), morning PEF (peak expiratory flow) (P=.004), evening PEF (P=.020), and percent rescue-free days (P=.002) at end point, and it significantly reduced nighttime symptom scores (P <.001) and mean total (P=.018), and nighttime (P <.001) albuterol use. Withdrawals from the study were more frequent with MON (21%) than with FP (13%). Adverse events (69% vs 71%) and mean end point to baseline 12-hour urinary cortisol excretion ratios were similar. Parents and physicians were more satisfied with FP treatment than with MON (P=.006 and P=.016, respectively, at Week 12). Mean total daily asthma-related cost per patient in the FP group was approximately one-third of that in the MON group ($1.25 vs $3.49). FP was significantly more effective than MON in improving pulmonary function, asthma symptoms, and rescue albuterol use. Both therapies had similar safety profiles. Parent- and physician-reported satisfaction ratings were higher with FP treatment, and asthma-related costs were lower.

Effect of ciclesonide and fluticasone on hypothalamicpituitary-adrenal axis function in adults with mild-to-moderate persistent asthma

Despite their proven efficacy in the treatment and prevention of asthma exacerbations, current inhaled corticosteroids carry safety concerns, especially adrenal suppression. Ciclesonide (hydrofluoroalkane propellant) is a novel inhaled corticosteroid with few, if any, clinical adverse events. To evaluate the potential effects of ciclesonide therapy on the dynamic cortisol response to sequential low- and high-dose cosyntropin stimulation in adults with mild-to-moderate persistent asthma. This was a double-blind, randomized, placebo-controlled, 12-week study in adults with mild-to-moderate asthma. One hundred sixty-four patients were randomized and treated; 148 patients completed the study. Fluticasone propionate (chlorofluorocarbon propellant) was used as an active comparator. The doses administered were 320 microg of ciclesonide once daily, 320 microg of ciclesonide twice daily, and 440 microg of fluticasone propionate twice daily, all doses ex-actuator. For both ciclesonide groups, changes in mean low- and high-dose peak serum cortisol levels and in 24-hour urinary free cortisol levels corrected for creatinine were small vs baseline and comparable with placebo. For the fluticasone propionate group, significant reductions vs placebo in serum cortisol levels in response to high-dose cosyntropin stimulation and in 24-hour urinary free cortisol levels were observed. Oral candidiasis rates were 2.5% for 320-microg/d ciclesonide, 2.4% for 640-microg/d ciclesonide, and 22.0% for 880-microg/d fluticasone propionate. These findings confirm the safety of ciclesonide therapy, demonstrating that at doses up to 640 microg/d, the drug does not affect sensitive markers of adrenal function.

Fluticasone Propionate HFA-134a Pressurized Metered-Dose Inhaler in Adolescents and Adults with Moderate to Severe Asthma

In this randomized, double-blind, placebo-controlled trial, 397 patients with moderate to severe asthma, previously treated with bronchodilators alone, received fluticasone propionate 88, 220, or 440 μg twice daily, or placebo via metered dose inhaler (MDI) for 12 weeks. Mean change from baseline to endpoint in pre-dose percent predicted forced expiratory volume in one second (FEV1) was greater (p < 0.001) in each fluticasone propionate group (9.0%, 88 μg bid; 9.8%, 220 μg bid; 11.2%, 440 μg bid) versus placebo (3.4%). Morning and evening peak expiratory flow (PEF), asthma symptoms, and supplemental albuterol use also improved in all fluticasone propionate groups versus placebo. The incidence of adverse events and 24-hour urine cortisol excretion rates were similar between active treatments and placebo.

Efficacy of fluticasone on cough: a randomised controlled trial

Cough may be the consequence of bronchial hyperresponsiveness (BHR) and inflammation. This study was designed to investigate the short-term effects of an inhaled steroid (fluticasone propionate (FP)) on cough, and to determine the effects of smoking, BHR, allergy and forced expiratory volume in one second (FEV1) on the efficacy of FP. In a community-based primary healthcare centre, 135 previously healthy adults suffering from cough for > or =2 weeks were enrolled in a randomised, double-blind, placebo-controlled trial of inhaled FP 500 microg b.i.d. for 2 weeks. Participants completed daily diary cards of lower respiratory tract symptoms. The primary outcome measure was the decrease in mean total daily cough score (0-6) during the second week of treatment. In the FP group, the cough score decreased from 3.8 at baseline to mean+/-SEM 1.4+/-0.2 during the second week. In the placebo group, this decrease was from 3.8 to 1.9+/-0.1 and was statistically significantly less. A favourable effect of FP was only detectable in nonsmokers, in whom the score was 0.9 points lower compared with placebo. The clinical relevance of this finding has to be established further. Allergy, FEV1 and BHR at baseline did not affect the efficacy of FP. In conclusion, anti-inflammatory treatment with the inhaled steroid fluticasone propionate reduces cough in otherwise healthy adults who do not smoke.

The effects of long term use of inhaled corticosteroids on linear growth, adrenal function and bone mineral density in children

In this study we aimed to investigate the long term effects of inhaled steroids on linear growth, adranal function and bone mineral density. Thirty children with moderate asthma were randomly divided into two groups.Fifteen children (8 boys, 7 girls mean age; 10.6 ± 2.1) were treated with budesonide (group 1), and 15 (9 boys, 6 girls, mean age; 9.6 ± 2.4). with fluticasone propionate (group 2). Control group included 30 children. Anthropometric assesment, symptom and medication scores, pulmonary functions, bone mineral density, serum and urine cortisol levels and ACTH stimulation test were evaluated at the beginning of the study and after one year period. Symptom and medication scores, pulmonary functions improved significantly in both groups (p < 0.05). The mean annual growth was similar in group 1 and 2 and control group. Bone mineral density was comperable with control group at the beginning of the study and after one year. Mean serum cortisol level diminished at the end of the therapy but no significant differences were found between the initial and end values in respect to urine cortisol levels and cortisole/creatinin ratio. Of three groups ACTH stimulation test revealed that there were no significant difference between stdy and control groups. In conclusion, although we did not observed any side effects of inhaled corticosteroids we suggest that children treated with inhaled corticosteroids for a long time should be followed closely with respect to side effects.

Effect of inhaled fluticasone propionate on BAL TGF-β 1 and bFGF concentrations in clinically stable lung transplant recipients

Background Inhaled fluticasone propionate (FP) therapy decreases inflammation and sub-basement membrane thickness in asthmatic airways. Bronchiolitis obliterans syndrome (BOS) in lung transplant recipients (LTRs) involves progressive airway fibrosis and obliteration. Therefore, augmented immunosuppression may be of some benefit in treating BOS. In this study, we examined the effect of 3 months of treatment with high-dose inhaled FP on the concentrations of 2 fibrogenic factors, transforming growth factor (TGF)–β 1 and beta fibrogenic growth factor (bFGF) in bronchoalveolar lavage (BAL) fluid from clinically stable LTRs. Methods We conducted a randomized, double-blind, placebo-controlled, parallel group study with inhaled FP (750 μg, twice/day for 3 months) in 28 LTRs (15 FP and 13 placebo). We recruited 23 healthy controls. We performed spirometry, bronchoscopy, and bronchoalveolar lavage procedures before treatment and after 3 months of treatment. We used commercially available enzyme-linked immunosorbent assay kits to measure BAL fluid TGF-β 1 and bFGF concentrations. Results In LTRs before treatment, BAL TGF-β 1 concentrations (but not bFGF concentrations), total cell counts, and neutrophil percentage increased compared with controls ( p < 0.05). We found no significant differences between FP and placebo groups at baseline measurements. After treatment, BAL TGF-β 1 concentrations significantly increased in the FP group ( p = 0.03), but we found no difference between FP and placebo groups; BAL bFGF concentrations increased during treatment in both groups compared with controls ( p < 0.05), but not significantly within either patient group ( p > 0.05). We found a reverse correlation between forced expiratory volume in 1 second (FEV 1) and BAL TGF-β 1 concentration in the FP group ( r = −0.53, p = 0.04), and between FEV 1 and BAL TGF-β 1 concentration in the placebo group ( r = −0.74, p = 0.004). Multivariable analysis indicated no significant independent effects of inhaled FP in either BAL TGF-β 1 or bFGF concentrations. Conclusions Bronchoalveolar fluid TGF-β 1 concentrations increased in LTRs after transplantation and may correlate with the decrease in lung function. Inhaled FP added to conventional immunosuppression had no effect on TGF-β 1 or bFGF production in BAL fluid.

Comparisons of two intranasal corticosteroid preparations in treating allergic rhinitis

Objectives Intranasal corticosteroid preparations can relieve symptoms of allergic rhinitis. Different aqueous corticosteroid forms have been developed for intranasal use. The objectives of this study were to compare efficacy and safety between fluticasone propionate and budesonide in the treatment for patients with allergic rhinitis. Methods The study was conducted in a prospective and randomized manner; a total of 24 adult patients were enrolled. All patients received MAST allergen test at entry and again at 2 months after treatments. Fourteen patients received fluticasone propionate 200 μg once daily, and 10 patients received budesonide 200 μg twice daily. To investigate the efficacy of fluticasone propionate and budesonide, a subjective scoring system was designed to evaluate the symptom improvement of patients. Adverse events were recorded on a diary card then were analyzed. Mann-Whitney U test and Kruskal-Wallis 1-way analysis of variance were used for statistical analysis. Results Analysis on patient-based symptom scores revealed that both fluticasone propionate and budesonide were equally efficacious in improving the symptoms of nasal blockage, sneezing, nasal itching, and watery rhinorrhea. There were no significant side effects reported for both groups during this follow-up period. However, analysis showed that the fluticasone propionate group demonstrated significantly greater improvement in some MAST allergen tests ( Candida, mite, house dust; P < 0.05). Conclusion Clinically, fluticasone propionate 200 μg once daily was efficacious as budesonide 200 μg twice daily in the relief of allergic rhinitis symptoms. However, fluticasone propionate can achieve greater immunologic improvement. Both preparations showed no evidence of short-term side effects.

Withdrawal From Treatment as an Outcome in the ISOLDE Study of COPD

To investigate the determinants of patient withdrawal from our study, and the effect of these withdrawals on the outcome of treatment with inhaled corticosteroids in patients with COPD. A double-blind, placebo-controlled, randomized trial. Eighteen outpatient centers in the United Kingdom. Seven hundred fifty-one patients with stable COPD defined clinically and as baseline postbronchodilator FEV(1) > or = 0.8 L and < 85% predicted, FEV(1)/FVC ratio < 70%, and FEV(1) change after albuterol < 10% of predicted. Random assignment of either 500 microg bid of inhaled fluticasone propionate (FP) using a spacer device or an identical placebo inhaler. Treatment was continued for 3 years or until patients withdrew from follow-up. Postbronchodilator FEV(1) was measured on three occasions before randomization and every 3 months thereafter. Health status was assessed by the disease-specific St. George Respiratory Questionnaire (SGRQ) and the modified short-form 36 questionnaire (SF-36) at baseline and every 6 months. Three hundred thirty-nine patients withdrew, of whom 156 patients received FP. Prescription of frequent courses of oral prednisolone was the most common reason for withdrawing as specified in the protocol (69 patients in the FP group withdrew due to respiratory symptoms, compared with 93 patients in the placebo group). This explained the significantly greater dropout of placebo-treated patients that was most evident when FEV(1) was < 50% predicted. Patients withdrawing had a significantly more rapid decline in health status, measured by both the SGRQ and the SF-36 (p < 0.001). Those withdrawing from the placebo group had a more rapid decline in FEV(1) and more exacerbations than the FP-treated groups. Baseline FEV(1) was lower in dropouts than in patients completing the study receiving placebo, but there was no difference between the respective groups receiving FP. Patients who withdrew from follow-up were those with the most rapidly deteriorating health status and lung function. Losing these patients from the final analysis can reduce the power of a study to achieve its primary end point.

Improvement in health‐related quality of life with fluticasone propionate compared with budesonide or beclomethasone dipropionate in adults with severe asthma

Changes in health-related quality of life (HRQoL) were evaluated in adults with severe asthma following inhaled corticosteroid treatment with high-dose beclomethasone dipropionate or budesonide (BDP/BUD) and compared with fluticasone propionate taken at approximately half the dose of BDP/BUD. HRQoL was assessed as part of an open, multicentre, randomized, parallel-group study in Australia evaluating the safety and efficacy of switching to fluticasone propionate (FP) 1000-2000 micro g/day (n = 67) compared with remaining on BDP/BUD >/=1750 micro g/day (n = 66) for 6 months. Patients completed two HRQoL questionnaires, the Asthma Quality of Life Questionnaire (AQLQ) and the Medical Outcomes Study Short Form-36 (SF-36), at baseline and at weeks 12 and 24. A change in AQLQ score of >/=0.5 was considered to be clinically meaningful. There were significant improvements in HRQoL with FP on four of the eight dimensions on the SF-36 (i.e. physical functioning, general health, role-emotional, and mental health), while there were no significant improvements in HRQoL in the BDP/BUD group. Overall, patients in the FP group experienced significantly greater improvement (P < 0.001) in AQLQ scores at weeks 12 and 24 compared with the BDP/BUD group. On the individual domains of the AQLQ, there were significant treatment differences (P < 0.01) in favour of FP in three of the four domains (activity limitations [0.92], symptoms [0.73], and emotional function [1.02]). Mean differences between groups for overall score and these three domains were also clinically meaningful. Patients with severe asthma who received FP (at approximately half the dose of BDP/BUD) experienced statistically significant, as well as clinically meaningful, improvements in their HRQoL.

The Positive Effects of Natural Capital and Tax Shifting on Cogeneration Project Economics Related to Greenhouse Gas Emissions

<h3>Background</h3> The aim of this work was to investigate the safety and efficacy of single-inhaler triple therapy with 12.5 μg glycopyrronium (GB)/12 μg formoterol fumarate (FF)/250 μg fluticasone propionate (FP), compared to 50 μg GB co-administered with a fixed dose of 12 μg FF/250 μg FP in subjects with COPD. <h3>Methods</h3> This was a phase 3, randomised, double-blind, active-control, parallel-group, noninferiority study conducted at 20 sites across India. COPD patients aged ≥40 to ≤75 years, with forced expiratory volume in 1 s (FEV₁)/forced vital capacity (FVC) &lt;0.70, using mono/dual therapy with inhaled corticosteroids (ICSs), long-acting muscarinic antagonists (LAMAs), or long-acting β-agonists (LABAs) for ≥1 month, were included. Subjects were randomised 1:1 to GB/FF/FP or GB+FF/FP for 12 weeks. The primary efficacy end-point was the change from baseline in trough FEV₁ at the end of 12 weeks. The study is registered with the Clinical Trials Registry of India (identifier number: CTRI/2019/01/017156). <h3>Results</h3> Between 23 March 2019 and 14 February 2020, 396 subjects were enrolled, with 198 patients each in the fixed-triple (GB/FF/FP) and open-triple (GB+FF/FP) groups. The difference in least-square mean (LSM) changes in pre-dose FEV₁ from baseline at 12 weeks was noninferior between the groups (p&lt;0.05). The LSM change from baseline in post-dose FEV₁ was comparable (p=0.38). A superiority test showed comparable efficacy (p=0.12) for the difference in mean change from baseline in trough FEV₁ between the groups. Adverse events (mild or moderate) were recorded in 25.3% and 24.9% of subjects in the GB/FF/FP and GB+FF/FP groups. <h3>Conclusions</h3> Fixed triple therapy with GB/FF/FP provides comparable bronchodilation and lung function improvement as open-triple therapy. It is safe and well tolerated in symptomatic COPD patients with a history of exacerbations.

Addition of salmeterol to fluticasone propionate treatment in moderate-to-severe asthma

This study was designed to determine whether the benefit of adding salmeterol was superior to doubling the dose of fluticasone propionate (FP) over 6 months, compared to a control group who remained on a lower dose of FP. The multi-centre, double-blind, parallel group study involved 496 symptomatic asthmatic patients with a history of exacerbations on 500–800 micrograms (μg) inhaled corticosteroids (ICS) twice daily (b.d.) in a broadly representative group of 100 hospitals and general practices in six countries. Two doses of FP—250 μg b.d. (FP250) or 500 μg b.d. (FP500)—were compared with the lower dose of FP plus a long-acting β 2-agonist, salmeterol 50 μg b.d. (SM/FP250). Patients symptomatic on the run-in dose of FP250 alone formed the control group in the treatment period. Over 6 months, SM/FP250 significantly improved mean morning peak expiratory flow rates (amPEF) by 42.1l/min, more than twice the improvement achieved with either dose of FP alone. SM/FP250 also resulted in more symptom-free days and nights ( P<0.002) and days and nights with no relief medication ( P<0.001). The number of severe exacerbations was low: 3, 6 and 8% in the SM/FP250, low- and high-dose FP groups, respectively. This study confirms that adding salmeterol to low-dose inhaled FP offers greater improvements than either maintaining or doubling the dose of FP. Significant benefit was gained from adding salmeterol in a group of patients who appeared to have been at the top of their steroid dose–response curve receiving FP250. There was no evidence of tolerance and a low incidence of exacerbations in all treatment groups.

Comparison of the efficacy of beclometasone dipropionate and fluticasone propionate suspensions for nebulization in adult patients with persistent asthma

The use of nebulization for the administration of inhaled steroids plays an important role in asthma patients who are unable to use pressurized aerosol or dry-powder inhalers effectively. Moreover, the type of nebulizer used may affect how much drug is delivered to the lungs. The objective of this multinational, multicentre, randomized, active controlled, parallel-group study was to compare the efficacy and safety of nebulized corticosteroids in adult patients with chronic asthma. Following a 1-week placebo run-in period, 205 patients, aged 18–65 years, with moderate persistent asthma were randomized to one of two treatment groups for 12 weeks: beclometasone dipropionate (BDP) suspension for nebulization 2400 μg day −1 b.i.d. ( n=103), or fluticasone propionate (FP) suspension for nebulization 2000 μg day −1 b.i.d. ( n=102), both administered by a jet nebulizer. Comparable efficacy in controlling asthma was demonstrated by the two treatments at study end, as evident when evaluating various efficacy parameters (pulmonary function tests, asthma exacerbations and symptoms, and the use of rescue salbutamol). The primary efficacy endpoint was the variation in the pulmonary expiratory flow (PEF) at treatment end over the baseline visit. For the intent-to-treat popoulation, in the BDP group mean PEF values increased statistically significantly from 5·2 ± 1·31 s −1 to 5·7 ± 1·61 s −1, while in the FP group the increase was from 5·2 ± 1·21 s −1 to 5·8 ± 1·81 s −1. Mean PEF values as per cent of predicted also increased in a statistically significant way, from 71% to 77·1% in the BDP group, and from 70·1% to 76·9% in the FP group. The two treatments were equally well tolerated. A total of 23 and 32 patients in the BDP and FP groups, respectively, reproted adverse events during the treatment period, and these were generally mild. In conclusion, the results of this study demonstrate that BDP 2400 μg day −1 and FP 2000 μg day −1, both suspensions for nebulization administered via a jet nebulizer, are equally effective, with an acceptable safety and tolerability profile, when used in adult patients with moderate persistent asthma.

Estimation of the dose of fluticasone propionate inhaled by infants after bronchiolitis: Effect on urinary cortisol excretion

Background: Information on the dose of steroid infants inhale from spacer devices and its potential effect on adrenal suppression is limited. Objective: We sought to determine the total dose of fluticasone propionate (FP) inhaled from a spacer device (Babyhaler) with face mask attachment by infants recovering from acute bronchiolitis and the effect of inhaled FP on the infants' overnight urinary cortisol/creatinine ratios (UCCRs). Methods: Infants studied were recovering from acute bronchiolitis. In study 1, 22 infants inhaled 150 μg of FP through the Babyhaler. The likely inhaled dose was estimated by trapping it on a filter held within the face mask. In study 2, 40 infants had UCCRs measured before and during 3 months of treatment with either FP (150 μg twice daily, n = 20) or placebo (n = 20). Results: In study 1 the mean ± SD dose of captured FP was 12.8 ± 6.9 μg (ie, 2.1 ± 1.2 μg/kg). In study 2 the pretreatment UCCR medians (interquartile ranges) were as follows: FP, 22.8 (23.0) nmol/mmol; placebo, 24.0 (28.3) nmol/mmol. Within- group UCCR changes (median and interquartile range Δ UCCR) were significantly different in the FP group (−8.9 and −20.6 nmol/mmol at 6 weeks and −12.6 and −25.9 nmol/mmol at 12 weeks, respectively; P = .0008) but not in the placebo group ( −5.8 and − 10.7 nmol/mmol at 6 weeks and +0.3 and − 17.9 nmol/mmol at 12 weeks, respectively; P = .45). Intergroup changes were insignificant in the follow-up period (6 weeks, P = .52; 12 weeks, P = .19). Conclusion: After bronchiolitis, infants are likely to inhale approximately 8 % of the nominal steroid dose from the Babyhaler. UCCRs can be used to monitor the bioavailability of inhaled steroids in young infants. (J Allergy Clin Immunol 2002;110:721-7.)

Transactivation Assay for Determination of Glucocorticoid Bioactivity in Human Serum

We have developed a mammalian cell (COS-1) bioassay, which measures glucocorticoid bioactivity (GBA) directly from a small amount of human serum. The assay is based on the expression of human glucocorticoid receptor (GR) together with a coactivator protein and reporter plasmid containing GR response elements upstream of the luciferase gene. Ten microliters of human serum, in duplicate, are added directly to the cell culture medium, and GBA is derived from reporter gene activity. The assay differentiates between biopotencies of synthetic steroids, and importantly, mifepristone (RU486) is able to block glucocorticoid-induced response. The assay is sensitive (<15.6 nm cortisol in fetal calf serum) and precise, with the within- and between-assay coefficients of variation less than 8% and 10%, respectively. We measured serum GBA (bioassay) and cortisol (RIA) levels in 34 asthmatic children (age range, 5.7–14.2 yr) at baseline and after treatment with either inhaled budesonide (800 μg/d, n = 14), fluticasone propionate (500 μg/d, n = 14), or cromones (control group, n = 6). Pretreatment serum GBA and cortisol levels correlated strongly (r = 0.90, P < 0.0001, n = 34). Two months of treatment with inhaled budesonide resulted in excess GBA in circulation, which was not attributable to endogenous cortisol (P < 0.001). In the fluticasone propionate group, the presence of serum excess GBA was at the borderline of statistical significance (P < 0.08) after 2 months of inhalation therapy, and no excess GBA was detected in the cromone group. In conclusion, our bioassay enables measurement of mammalian cell response to bioactive glucocorticoids in circulation and provides a novel means to investigate patients receiving drugs acting through the GR.

Biochemical markers of bone metabolism in relation to adrenocortical and growth suppression during the initiation phase of inhaled steroid therapy.

Growth suppression is usually most evident during the first year of inhaled steroid therapy. Steroid-induced changes in bone metabolism may contribute to this growth suppression. The aim of the present study was to evaluate the changes in biochemical markers of bone metabolism in relation to adrenal and growth suppression during the initiation phase of inhaled steroid therapy. Seventy-five school-aged children with new asthma were enrolled into budesonide (BUD, n = 30), fluticasone propionate (FP, n = 30) or cromone (CROM, n = 15) treatment groups. BUD dose was 800 microg/d during the first two months and 400 microg/d thereafter. The respective FP doses were 500 and 200 microg/d. Biochemical markers of bone metabolism were measured before treatment and after 2 and 4 mo of therapy. In the control (CROM) group, the mean concentrations of serum osteocalcin (OC), carboxyterminal propeptide of type I procollagen (PICP) (formation markers) and type I collagen carboxyterminal telopeptide (ICTP) (degradation marker) tended to increase. In the BUD group, OC and PICP decreased during the 4 mo by a mean of 23% (p < 0.001) and 15% (p < 0.05), respectively, while ICTP did not change significantly. In the FP group, OC and ICTP decreased during the first 2 mo by a mean of 19% (p < 0.01) and 21% (p < 0.01), respectively, returning to the pretreatment level at 4 mo, while PICP tended to increase during the 4 mo (14%, p = 0.12). In the steroid treated children whose height SD score decreased during the first 12 mo of therapy, both OC and PICP decreased during the first 4 mo by a mean of 20% (p < 0.01) and 21% (p < 0.001), respectively. In those children who had no growth suppression, the changes were not significant: -4% in OC and +13% in PICP. Furthermore, in children who developed evidence of adrenocortical suppression (on the basis of a low-dose ACTH test), OC decreased more (23%, p < 0.01) than in those with normal adrenocortical function (10%, p = 0.06). In conclusion, both inhaled BUD and FP caused dose-dependent effects on biochemical markers of bone metabolism. The children who developed growth or adrenocortical suppression were likely to have changes also in bone metabolism.

Biochemical Markers of Bone Metabolism in Relation to Adrenocortical and Growth Suppression During the Initiation Phase of Inhaled Steroid Therapy

Growth suppression is usually most evident during the first year of inhaled steroid therapy. Steroid-induced changes in bone metabolism may contribute to this growth suppression. The aim of the present study was to evaluate the changes in biochemical markers of bone metabolism in relation to adrenal and growth suppression during the initiation phase of inhaled steroid therapy. Seventy-five school-aged children with new asthma were enrolled into budesonide (BUD, n = 30), fluticasone propionate (FP, n = 30) or cromone (CROM, n = 15) treatment groups. BUD dose was 800 μg/d during the first two months and 400 μg/d thereafter. The respective FP doses were 500 and 200 μg/d. Biochemical markers of bone metabolism were measured before treatment and after 2 and 4 mo of therapy. In the control (CROM) group, the mean concentrations of serum osteocalcin (OC), carboxyterminal propeptide of type I procollagen (PICP) (formation markers) and type I collagen carboxyterminal telopeptide (ICTP) (degradation marker) tended to increase. In the BUD group, OC and PICP decreased during the 4 mo by a mean of 23% (p < 0.001) and 15% (p < 0.05), respectively, while ICTP did not change significantly. In the FP group, OC and ICTP decreased during the first 2 mo by a mean of 19% (p < 0.01) and 21% (p < 0.01), respectively, returning to the pretreatment level at 4 mo, while PICP tended to increase during the 4 mo (14%, p = 0.12). In the steroid treated children whose height SD score decreased during the first 12 mo of therapy, both OC and PICP decreased during the first 4 mo by a mean of 20% (p < 0.01) and 21% (p < 0.001), respectively. In those children who had no growth suppression, the changes were not significant: −4% in OC and +13% in PICP. Furthermore, in children who developed evidence of adrenocortical suppression (on the basis of a low-dose ACTH test), OC decreased more (23%, p < 0.01) than in those with normal adrenocortical function (10%, p = 0.06). In conclusion, both inhaled BUD and FP caused dose-dependent effects on biochemical markers of bone metabolism. The children who developed growth or adrenocortical suppression were likely to have changes also in bone metabolism.

Cost-Effectiveness of Fluticasone Propionate Administered Via Metered-Dose Inhaler Plus Babyhaler™ Spacer in the Treatment of Asthma in Preschool-Aged Children

To evaluate the cost-effectiveness of inhaled fluticasone propionate (FP) in children aged 12 to 47 months with asthma symptoms. A retrospective economic analysis conducted from the perspective of the Danish health-care system, based on clinical data from a 12-week study. Thirty-three outpatient centers in nine countries. Two hundred thirty-seven children aged 12 to 47 months with documented history of recurrent wheeze or asthma symptoms. Two dosages of FP, 100 microg/d and 200 microg/d, and placebo administered in two divided doses via a metered-dose inhaler and a Babyhaler (Glaxo Wellcome; Middlesex, UK) spacer device. Effectiveness in terms of asthma exacerbations, control of cough and wheeze symptoms, symptom-free days, overall direct costs of asthma management in Danish kroner at 1999 prices, and mean and incremental cost-effectiveness ratios. FP, 200 microg/d, was significantly more effective than placebo treatment in terms of the proportion of exacerbation-free patients (73.7% vs 59.8%; p = 0.025) and patients experiencing a > or = 25% improvement in cough symptoms (57.9% vs 39.0%; p = 0.018). The costs per exacerbation-free patient, per patient with a > or = 25% improvement in cough and wheeze symptoms from baseline, and per symptom-free day were lower in the FP groups than in the placebo group. The incremental cost-effectiveness ratios for these end points indicated that the additional benefits of FP, 200 microg/d, were achieved at a lower overall cost compared with placebo treatment. From the perspective of the Danish health-care system, FP, 100 microg bid, administered via the Babyhaler inhalation device was cost-effective relative to standard therapy with bronchodilators alone.

Serum Dehydroepiandrosterone Sulfate Concentration as an Indicator of Adrenocortical Suppression in Asthmatic Children Treated with Inhaled Steroids

ACTH regulates adrenal androgen production, which may thus be reduced during glucocorticosteroid therapy. Dehydroepiandrosterone sulfate is the most abundant androgen secreted by the adrenals. We wished to evaluate whether serum levels of dehydroepiandrosterone sulfate can be used as an indicator of adrenal suppression during inhaled steroid treatment in children. Sixty school-aged children with newly diagnosed asthma were randomly divided into budesonide (n = 30) and fluticasone propionate (n = 30) groups. Fifteen cromone-treated children served as a control group. The budesonide dose was 800 μg/d during the first 2 months and 400 μg/d thereafter. The respective fluticasone propionate doses were 500 and 200μ g/d. Serum dehydroepiandrosterone sulfate concentrations were measured before and after 2 and 4 months of treatment. In the budesonide group, serum dehydroepiandrosterone sulfate decreased from the baseline by a mean of 21% (95% confidence interval, 13–29%; P < 0.001) after 2 months of high dose treatment and by 16% (95% confidence interval, 8–25%; P < 0.001) after 4 months of treatment. In the fluticasone propionate group, the respective figures were 10% (95% confidence interval, 4–16%; P < 0.01) and 6% (95% confidence interval, 16% decrease–3% increase; P = NS). A low dose ACTH test indicated adrenocortical suppression at 4 months in 14 (23%) steroid-treated children. In these children, dehydroepiandrosterone sulfate decreased by a mean of 21% (95% confidence interval, 14–28%), whereas in those 46 steroid-treated children with normal ACTH test results, dehydroepiandrosterone sulfate decreased by 8% (95% confidence interval, 0–16%; P < 0.05 between these groups). In the control group, dehydroepiandrosterone sulfate levels tended to increase (by a mean of 26%), reflecting the normal physiological change at this age. In conclusion, inhaled steroid treatment suppresses dehydroepiandrosterone sulfate production in a dose-dependent manner. Monitoring of serum dehydroepiandrosterone sulfate concentrations can be used as a practical method to follow adrenocortical function and to detect its suppression during inhaled steroid treatment in children.