Dose Of Beclomethasone Dipropionate Research Articles

Assessment of extrafine beclomethasone/formoterol for the treatment of chronic obstructive pulmonary disease: A non-interventional study in a Bulgarian population

BackgroundThe beneficial effects of application of a fixed dose beclomethasone dipropionate (BDP) and formoterol fumarate (F) for the treatment of severe chronic obstructive disease (COPD) has been amply proven in well controlled clinical trials. Whether this also holds for real-world conditions and in such a heterogeneous patient population as is encountered in Bulgaria remained to be investigated. MethodsIn an observational, non-interventional study, 441 Bulgarian patients with severe COPD who were enrolled at 36 sites across the country received extrafine BDP/FF-combination therapy using the NEXThaler® DPI or the Foster® pMDI over a period of 16 weeks. At visits at the beginning, after 4 weeks and at the end of the study, alterations in lung function parameters FEV1 and FVC, disease symptoms, changes in CAT score, and patient distribution in GOLD 2017 categories A through D were assessed. ResultsA large share of the Bulgarian patients with severe COPD suffered from serious comorbidities, received additional medication, and about 2/3 were former or current smokers. Extrafine BDP/FF caused an increase in mean FEV1, FVC, a decrease of health impact as assessed by the CAT score, and a considerable shift of the share of category C and D patients towards A and B. In addition, the percentage of patients that were free of symptoms impacting everyday life such as fatigue and shortness of breath at rest increased throughout the study. A comparison of both application devices indicated that the NEXThaler® was superior in terms of lung functional aspects, as these parameters displayed a constant improvement over the observation period, whereas they plateaued at week 4 when using the pMDI. ConclusionsThe therapeutic benefits of extrafine BDP/FF known from clinical trials could also be observed in a real-world setting, even in such a heterogenous patient population as the Bulgarian. The NEXThaler® appeared to be highly efficient in this setting, opening a new choice for the lung specialist and the patient to select the one device considered most suitable and practical.

Determinants of asthma control and exacerbations in moderate to severe asthma

Determinants of asthma control and exacerbations in moderate to severe asthma

Impact of body mass index on omalizumab response in adults with moderate-to-severe allergic asthma

BackgroundEffectiveness of asthma treatment, including biologics, may be different in patients with higher body mass index (BMI). ObjectiveTo evaluate response to omalizumab (dosed by serum immunoglobulin E level and weight) by BMI category. MethodsPooled data from 2 randomized, double-blind, placebo-controlled studies of adults with moderate-to-severe allergic asthma were analyzed by BMI category (<25 kg/m2 [normal or underweight], n = 397; 25 to <30 kg/m2 [overweight], n = 330; ≥ 30 kg/m2 [obese], n = 268). Placebo-adjusted exacerbation rate reductions were evaluated by Poisson regression modeling. Changes from baseline in forced expiratory volume in 1 second, beclomethasone dipropionate (BDP) dose, Total Asthma Symptom Score, and Asthma Quality of Life Questionnaire were evaluated by analysis of covariance. ResultsGreater placebo-adjusted exacerbation rate reductions (95% confidence interval) were observed with increasing BMI (normal or underweight, −37.4% [−69.0% to 26.8%]; overweight, −52.7% [−78.4% to 3.7%]; obese, −71.9% [−86.9% to −39.5%]). There were no differences in forced expiratory volume in 1 second improvement between BMI categories at week 16 (normal or underweight, 76.2 [5.3-147.1] mL; overweight, 98.1 [13.9-182.4] mL; obese, 69.1 [−18.9 to 157.2] mL). No differences in BDP dose reduction (µg) were noted between BMI categories (normal or underweight, 23.0 [15.7-30.3]; overweight, 22.5 [13.5-31.5]; obese, 16.6 [5.8-27.3]). Fewer patients in the higher BMI categories eliminated BDP use. There were trends for smaller improvements with higher BMI in Total Asthma Symptom Score (normal/underweight, −0.52 [−0.82 to −0.22]; overweight, −0.50 [−0.80 to −0.20]; obese, −0.39 [−0.77 to 0.00]) and Asthma Quality of Life Questionnaire (normal or underweight, 0.34 [0.16-0.52]; overweight, 0.34 [0.13-0.55]; obese, 0.15 [−0.08 to 0.39]). ConclusionOmalizumab provides benefit to patients with moderate-to-severe allergic asthma, regardless of BMI. Trial RegistrationStudies 008/009 were conducted before clinical trial registration was required, and therefore clinical trial registration numbers are not available.

ВЛИЯНИЕ ДЛИТЕЛЬНОЙ КИСЛОРОДОТЕРАПИИ НА КЛИНИЧЕСКОЕ ТЕЧЕНИЕ ЗАБОЛЕВАНИЯ И ФУНКЦИЮ ДИАФРАГМЫ У БОЛЬНЫХ ХРОНИЧЕСКОЙ ОБСТРУКТИВНОЙ БОЛЕЗНЬЮ ЛЕГКИХ С ГИПОКСЕМИЧЕСКОЙ ДЫХАТЕЛЬНОЙ НЕДОСТАТОЧНОСТЬЮ (ОПЫТ ТРЕХЛЕТНЕГО НАБЛЮДЕНИЯ)

The objective: to determine the effect of prolonged oxygen therapy (POT) on changes in the clinical and functional status of patients with chronic obstructive pulmonary disease (COPD) and severe hypoxemic chronic respiratory failure. Subjects and methods. 30 patients with COPD were examined during the period of remission of the disease, the average age was 64.8 ± 6.9 years. After the initial examination, patients were prescribed POT at home for 16 hours/day. As a basic therapy, all patients received a combined bronchodilator of long-acting indacaterol/glycopyrronium at a dose of 110/50 μg once a day in combination with beclomethasone dipropionate (BDP) at the dose of 200-400 μg/day. The patients were examined repeatedly 3 times with a 1-year interval. Clinical indicators, gas composition of arterial blood, results of spirometry and ultrasound examination of the diaphragm were evaluated. Results. Initially, disorders of the functional state of the diaphragm were detected in COPD patients with hypoxemia (decrease in the thickening fraction and relaxation rate). After the first year of using POT, an increase in the rates of contraction and relaxation of the diaphragm muscle under tidal respiration was observed. On the 2nd and 3rd year of using POT, it was noted that indicators of the functional state of the diaphragm stabilized. As a result of POT, the number of exacerbations went down and mortality in COPD patients with hypoxemia decreased. Against the background of basic therapy with indacaterol/glycopyrronium in combination with low doses of BDP, no adverse events were observed for the entire period of follow-up. Conclusions. POT in combination with a double long-acting bronchodilator and low-dose inhaled glucocorticosteroids in COPD patients with hypoxemic chronic respiratory failure helps to reduce dyspnea, the number of severe exacerbations, as well as improve pulmonary ventilation functions, blood gas content, and the diaphragm function during the first year of its use. Further, the indicators continued to stabilize.

The effect of body posture during medication inhalation on exercise induced bronchoconstriction in asthmatic children

RationaleInhaling medication in a standard body posture leads to impaction of particles in the sharp angle of the upper airway. Stretching the upper airway by extending the neck in a forward leaning body posture may improve pulmonary deposition. A single dose of inhaled corticosteroids (ICS) offers acute, but moderate protection against exercise induced bronchoconstriction (EIB). This study investigated whether inhaling a single dose of ICS in a forward leaning posture improves this protection against EIB. Methods32 Asthmatic children, 5–16 years, with EIB (Median fall in FEV1 or FEV0.5 30.9%) performed two exercise challenge tests (ECT's) with spirometry in a single blinded cross-over trial design. Children inhaled a single dose of 200 μg beclomethasone dipropionate (BDP) 4 h before the ECT, once in the standard posture and once with the neck extended in a forward leaning posture. Spirometry was also performed before the inhalation of the single dose of BDP. ResultsInhalation of BDP in both body postures provided similar protection against EIB (fall in FEV1 or FEV0.1 in standard posture 16.7%; in forward leaning posture 15.1%, p = 0.83). Inhaling ICS in a forward leaning posture significantly delayed EIB compared to inhaling in the standard posture (respectively 2.5 min ± 1.0 min vs. 1.6 min ± 0.8 min; difference 0.9 min (95CI 0.25; 1.44 min); p = 0.01). ConclusionInhalation of a single dose BDP in both the forward leaning posture and the standard posture provided effective and similar protection against EIB in asthmatic children, but the forward leaning posture resulted in a delay of EIB. RegisterNTR3432 (www.trialregister.nl).

Oral high dose Beclomethasone dipropionate for treatment of active ulcerative colitis

Oral corticosteroids (CS) have been widely used for treatment of ulcerative colitis (UC) at the price of systemic side effects. Role of topically active oral beclomethasone dipropionate (BDP) in clinical practice is still unclear. The aim of this paper is to investigate efficacy and tolerability of a high dose BDP regimen in mild to moderately active UC. Twenty-five patients (9 males, aged 25-40 years) with mild to moderately active UC, unresponsive to oral and topical 5-ASA (4.8 gr daily) and BDP (5 mg daily), were enrolled. All patients continued 5-ASA plus high dose oral BDP (15 mg od for 4 weeks and than tapered). Clinical, endoscopic, histological and laboratory parameters were monitored. Mean disease activity index (DAI) score at study entry was 8.82±4. Response to treatment was observed in all patients after 2 weeks. Remission was observed in all patients within 4-6 weeks from entering the study (mean DAI score: 2.34±0.5) and maintained throughout 6-month follow-up. No major adverse events were documented. Quality of life global evaluation score improved. This study provides the first evidence of efficacy and safety of high dose oral BDP-scheme in UC demonstrating excellent tolerability and favourable acceptability profile. This new BDPscheme might be a valid alternative to conventional oral CS when standard dose BDP is not effective. Future studies are needed to explore further clinical indications.

The effect of inhaled corticosteroids on hypothalamic-pituitary-adrenal axis

Objectives:The aim of this study was to compare systemic effects of high-dose fluticasone propionate (FP) and beclomethasone dipropionate (BDP) via pressurized metered dose inhaler on adrenal and pulmonary function tests.Materials and Methods:A total of 66 patients with newly diagnosed moderate persistent asthma without previous use of asthma medications participated in this single blind, randomized, parallel design study. FP or BDP increased to 1 500 μg/d in 62 patients who had not received oral or IV corticosteroids in the previous six months. Possible effects of BDP and FP on adrenal function were evaluated by free cortisol level at baseline and after Synacthen test (250 μg). Fasting plasma glucose and pulmonary function tests were also assessed. Similar tests were repeated 3 weeks after increasing dose of inhaled corticosteroids to 1 500 μg/d.Results:No statistically significant suppression was found in geometric means of cortisol level post treatment in both groups. After treatment in FP group, mean forced expiratory volume in one second (FEV1) and mean forced vital capacity (FVC) values improved by 0.17 l (5.66% ± 13.91, P=0.031) and 0.18 l (5.09% ± 10.29, P=0.010), respectively. Although FEV1 and FVC improved in BDP group but was not statistically significant. Oral candidiasis and hoarseness were observed in 6.5% patients receiving BDP, but hoarseness was found in 3.2% patients in FP group (P=0.288).Conclusions:The results indicate that safety profiles of high doses of BDP and FP with respect to adrenal function are similar, but FP is more efficacious than that of BDP in improving pulmonary function test.

AERODYNAMIC CHARACTERIZATION OF BECLOMETHASONE DIPROPIONATE FROM BECLATE-50 INHALER® BY HPLC-UV

A simple yet sensitive high performance liquid chromatography (HPLC) method was developed and validated for the determination of aerodynamic characteristics of the emitted dose of beclomethasone dipropionate from Beclate-50 Inhaler®. The mobile phase consisted of a mixture of acetonitrile and 10 mM ammonium acetate (70:30% v/v) adjusted to pH 5 with orthophosphoric acid. The HPLC analysis was run at a flow rate of 1 mL/min using a C18 column at a UV detection wavelength of 254 nm. The method was validated for specificity, linearity, precision, accuracy, limit of quantification, limit of detection, robustness, and solution stability. The calibration curve was linear over a concentration range of 0.03–62.50 µg/mL (r2 = 0.9999) with limit of detection and limit of quantification of 0.01 and 0.03 µg/mL, respectively. The intra-day and inter-day precision and accuracy were between 0.02 and 1.89% and −1.08 and 2.62%, respectively. The method was successfully applied to the aerodynamic characterization of both the fine particle and the emitted doses of beclomethasone dipropionate from Beclate-50 Inhaler®.

Effects of beclomethasone and factors related to asthma on the growth of prepubertal children

Few studies on the concomitant effects of beclomethasone dipropionate and asthma-related factors on the growth of prepubertal asthmatic children have been published to date. In this prospective long-term 'real-life' cohort study we recruited 82 prepubertal steroid-naïve asthmatic patients aged 3 + years, excluding those with birth weight lower than 2500 g, malnutrition, and other concurrent chronic diseases. Height/age and weight/age Z scores were calculated every three months. Random effects multivariate longitudinal data analysis was used to adjust height/age and weight/age Z scores with independent variables. Among the studied patients, 63.4% were male, aged 4.7 + or - 1.5 years, 68.3% suffered from severe persistent asthma and had normal values for height/age and weight/age Z scores at enrolment. They were followed for 5.2 years (range 2.3-6.1) and used a mean daily beclomethasone dipropionate dose of 351.8 mcg (range 137.3-1140.0). Height/age and weight/age Z scores were not affected by either duration of treatment or doses of beclomethasone dipropionate up to 500 mcg, 750 mcg and higher than 750 mcg (p-values > 0.17). The multivariate analysis final model showed that severe persistent asthma was associated to lower height for age Z score (p = 0.04), whereas hospitalizations because of acute asthma (before and during follow-up) were associated (p = 0.02) to lower weight for age Z score. Growth parameters were not affected by the use of beclomethasone dipropionate.

The clinical benefit of high dose inhalation therapy with beclomethasone dipropionate for patients with chronic bronchial asthma

Conventional doses of aerosolized beclomethasone dipropionate (BDP) of up to 400 micrograms/day by inhalation has often failed to normalize the pulmonary function of chronic adult patients. Therefore it may be necessary to administer the individual maximum dose of BDP to reduce bronchial inflammation. In 13 patients (2 males and 11 females, mean age 49.2 +/- 3.7 years old) with chronic asthma whose minimum %PEFRs were lower than 80% under treatment with conventional doses of BDP, the clinical benefit of high dose inhalation therapy with BDP was studied for four consecutive weeks by comparing % peak expiratory flow rate (%PEFR) measured four times a day both before and 10 minutes after inhaled procaterol (PCR) in a cross-over fashion. Mean morning %PEFRs before inhaled PCR during the first two weeks with a lower dose of BDP (419 +/- 24 micrograms/day) and during the following two weeks with a higher dose of BDP (904 +/- 55 micrograms/day) were 60.6 +/- 3.1% and 77.5 +/- 4.1%, respectively (p less than 0.01). Average increases in %PEFR during the higher dose period before and after inhaled PCR were 12.1% and 12.4%, respectively, which was observed by the end of the first week after the start of higher dose of BDP in 12 out of 13 patients. Since there were no adverse reactions such as hoarseness, oral thrush and candidiasis during the period with higher doses of BDP, it was concluded that we should promptly employ higher doses of BDP in patients who did not respond satisfactorily to conventional doses of BDP.

High dose steroid inhalation therapy using a large spacer: laboratory and clinical study on usefulness of the 4-puffs/inhalation method

We investigated whether or not the inhalation method of beclomethasone dipropionate (BDP) influences patient compliance and the clinical effects of therapy in chronic bronchial asthma, together with a basic study on the lung deposition of BDP using a twin Impinger when various numbers of puffs were discharged into three different spacers (Volumatic, InspirEase, Aerochamber). It was clearly shown that only the spacer, Volumatic maintained a high deposition rate of BDP in the lung model with a dose of 4-puffs/inhalation. Eighteen chronic asthmatic patients were studied. The patients inhaled BDP (800-1600 micrograms/day) by 1-puff/inhalation using a large spacer, Volumatic, for 12 weeks, and they then inhaled the same dose of BDP as given in the previous period by 4-puffs/inhalation using the spacer for 16 weeks. We compared the compliance of BDP, attack score, %PEFR and frequency of beta-agonist inhalation between these two periods. The compliance of BDP was markedly improved after changing from 1-puff/inhalation (92.8%) to 4-puffs/inhalation (99.8%). In the 4-puffs/inhalation period, attack score and %PEFR were significantly improved as compared to the 1-puff/inhalation period. The frequency of beta-agonist inhalation use in the 4-puffs/inhalation period was significantly lower than that in the 1-puff/inhalation period. These results indicate that when high dose steroid inhalation is given with a large spacer in chronic asthmatic patients, we should advice them of the appropriate inhalation method in order to obtain good compliance and clinical effects.

Acute Effects of Beclomethasone on Hyperpnea-Induced Bronchoconstriction

The aim of this study was to assess whether a single high dose of beclomethasone dipropionate (BDP) could blunt mast cell activation and bronchoconstriction after eucapnic voluntary hyperpnea (EVH). In this model of exercise-induced bronchoconstriction (EIB), seven athletes with EIB and eight untrained subjects with mild asthma performed two EVH tests 5.5 h apart on the same day; the first challenge after inhalation of a placebo aerosol and the second 4 h after inhalation of BDP (1500 microg). Prechallenge and postchallenge pulmonary function and urinary excretion of the mast cell mediator 9alpha, 11beta-prostaglandin (PG) F2 were followed, as well as urinary excretion of the bronchoconstrictor leukotriene (LT) E4. The EVH-induced bronchoconstriction was inhibited by BDP in both groups (P < 0.001): in athletes, mean +/- SEM percent fall in forced expiratory volume in 1 s was 22% +/- 4% after placebo versus 13% +/- 3% after BDP; in subjects with asthma, 23% +/- 4% after placebo versus 14 +/- 3% after BDP. This inhibition of airway response was associated with a significant reduction in the urinary excretion of 9alpha,11beta-PGF2 (P = 0.039) and LTE4 (P = 0.003) in both groups. Significant correlations were found between the percent fall in forced expiratory volume in 1 s and the increase in urinary excretion of both mediators 9alpha,11beta-PGF2 (r = 0.544, P = 0.002) and LTE4 (r = 0.380, P = 0.038) after EVH. We conclude that a single dose of BDP has an acute protective effect on the bronchial response to hyperpnea in both untrained subjects with asthma and athletes with EIB. This effect was associated with decreased excretion of urinary mediators, suggesting that BDP blunted the mast cell activation.

Dose–response relationship of inhaled corticosteroids and cataracts: A systematic review and meta‐analysis

The risk of cataracts associated with the long-term use of inhaled corticosteroids (ICS) is poorly recognized, yet may be of major public health importance. The aim of this study was to determine the dose-response relationship of ICS use and risk of cataracts in adults. A systematic review and meta-analysis was performed of case-control studies of cataracts and ICS use, which included at least two doses of ICS and in which the number of cases and controls using each dose of ICS was reported. The primary outcome variable was risk of cataracts. Four case-control studies were identified, with a total of 46 638 cases and 146 378 controls. There was a significant relationship between the risk of cataracts and ICS dose, with a random effects pooled odds ratio for risk of cataracts per 1000 microg increase in daily beclomethasone dipropionate dose of 1.25 (95% CI: 1.14-1.37). The risk of cataracts was increased by approximately 25% for each 1000 microg per day increase in the dose of beclomethasone dipropionate or equivalent. These findings reinforce the importance of prescribing within the therapeutic dose-response range for ICS in asthma and the need to determine the dose-response relationship for the efficacy of ICS in COPD. Screening for the presence of cataracts could usefully be undertaken in older subjects with asthma and COPD, particularly current or ex-smokers.

Dose–response relationship for risk of non‐vertebral fracture with inhaled corticosteroids

To determine the strength of association between the dose of inhaled corticosteroids (ICS) and risk of non-vertebral fracture in adults. A systematic review and meta-analysis of case-control studies of non-vertebral fractures in adults, in which at least two doses of ICS were reported as the dose of beclomethasone dipropionate (BDP) or equivalent. Five case-control studies were identified, with a total of 43 783 cases and 259 936 controls. There was an association between the risk of non-vertebral fracture and increasing dose of BDP. The random-effects odds ratio of relative risk for a non-vertebral fracture was 1.12 (95% confidence interval 1.00-1.26) per 1000 microg increase in the daily dose of BDP or equivalent. In older adults, the relative risk of non-vertebral fractures increases by about 12% for each 1000 microg/day increase in the dose of BDP or equivalent. The magnitude of this risk was considerably less than other common risk factors for fracture in the older adult.

Zileuton added to low-dose inhaled beclomethasone for the treatment of moderate to severe persistent asthma

To assess the therapeutic effects of oral zileuton tablets combined with low-dose beclomethasone compared to doubling the dose of beclomethasone, in improving lung function and reducing asthma symptoms. Randomized, active-control, double-blind, parallel, multi-center study of zileuton (400 or 600 mg QID)+200 microg beclomethasone dipropionate (BDP) BID versus placebo+BDP 400 microg BID in asthmatics with baseline FEV(1) percent predicted values between 40% and 80% following a single-blind ICS (BDP 200 microg BID) 2-week run-in. During the 3-month double-blind treatment period, assessments included safety, daytime and nighttime symptoms, acute asthma exacerbations, beta(2)-agonist use, AM and PM peak expiratory flow (PEF) and FEV(1). The addition of a 5-lipoxygenase (5-LO) inhibitor added to a low-dose of BDP showed no significant difference in FEV(1) compared to doubling the dose of BDP. FEV(1) improved in all 3 treatment groups, with mean increases of 10% with zileuton 600 mg QID+BDP 200 microg BID, 12% with zileuton 400mg QID+BDP 200 microg BID, and 11% with BDP 400 microg BID by study end. Within each treatment group, there were significant improvements in asthma symptoms and AM and PM PEF compared to baseline. No significant differences were observed between groups with regards to salbutamol use, acute asthma exacerbations, the requirement for oral/parenteral corticosteroids and adverse clinical events. The addition of a 5-LO inhibitor added to low-dose beclomethasone may be an alternative to higher-doses of ICS in patients unable to achieve sufficient asthma control on low-dose ICS therapy.

Clinical equivalency of Beclasone Eco Easi Breathe and Flixotide via MDI in asthma patients

It is well known that efficacy of asthma treatment depends on a choice of a basic medication as well as on a delivery system. The aim of this study was a comparison of clinical efficacy of equal doses of beclomethasone dipropionate (Beclasone Eco Easi Breathe) and fluticasone propionate (Flixotide) via MDI. The study was designed as a randomized open prospective comparative trial. Findings of 26 patients with moderate and severe asthma of &gt; 18 yrs old were analyzed, such as medical history, physical findings, spirometric and bronchodilating test results, heart beat rate and blood pressure, quality of life (QoL) using Russian version of AQLQ questionnaire. After the run-in period the patients randomly received Beclasone Eco Easi Breathe 500 to 1000 μg daily or Flixotide at the same doses for 4 weeks followed the cross-over change of the drugs for the next 4 weeks. After 1 month of the treatment, significant improvements in airflow parameters, need in short-acting β2 -agonists and QoL have been reported. After changing the drugs these effects have been maintained with no further reliable improvement. Thus, the study demonstrated similar efficacy and safety of these inhaled steroids that could be considered as being clinically equal in treatment of moderate and severe asthma.

Comparison of the efficacy and safety of budesonide turbuhaler administered once daily with twice the dose of beclomethasone dipropionate using pressurised metered dose inhaler in patients with mild to moderate asthma

Current treatment guidelines have clearly defined the central place and benefits of inhaled glucocorticoids in the management of bronchial asthma. However, compliance with therapy is often poor due to complexity of treatment regimens. Therefore, a single once daily regimen with a simple device, the turbuhaler might be expected to result in improved compliance and better efficiency. This was a prospective open randomized trial with parallel groups conducted in five tertiary medical institutions. Asthmatic patients who met the enrolment criteria were randomized to receive either budesonide 400 microg daily or beclomethasone dipropionate 400 microg twice daily for eight weeks. At the end of the study, both drugs were found to be effective in reducing the symptoms of asthma, reduction of beta2 agonist usage and improvement in lung function tests. However Budesonide Turbuhaler provided better effects in all parameters (p < 0.05). Both drugs were well tolerated. It is therefore concluded that Budesonide Turbuhaler administered once daily at a dose of 400 microg is more efficacious than Beclomethasone dipropionate 400 microg twice daily administered via pressurized metered dose inhaler.

Predicting Response to Omalizumab, an Anti-IgE Antibody, in Patients With Allergic Asthma

To determine baseline characteristics predictive of response to omalizumab, an anti-IgE antibody, in patients with allergic asthma. Pooled analysis of two multicenter, double-blind, randomized, placebo-controlled phase III studies with omalizumab. One thousand seventy allergic asthma patients symptomatic despite moderate-to-high doses (mean, 725 micro g/d) of inhaled beclomethasone dipropionate (BDP). Omalizumab (n = 542) or placebo (n = 528) were administered at a 4-weekly subcutaneous dose of at least 0.016 mg/kg/IgE (IU/mL) for 16 weeks in addition to stable BDP therapy. Univariate logistic regression was performed to explore baseline variables predictive of best response. Various aspects of response (reduced symptom scores, reduced usage of rescue medication, improved lung function, improved quality of life [QoL]) were explored as well as a composite definition of response (response in at least one of these four aspects with no asthma exacerbation during 16 weeks of treatment). Time to onset of response as well as the ability to predict eventual response were also determined for the composite definition of response. A consistent pattern of predictive covariates was seen over all definitions of response (except for QoL). For the composite definition, a history of emergency asthma treatment in the past year was the factor most predictive (p = 0.015) of best response on active treatment (response rate for those with such history was 67% for omalizumab and 42% for placebo; for those without a history the response rates were 63% and 54%, respectively). Another factor predictive of best response on active treatment was high BDP dose (p = 0.037; response rate for those treated with >or= 800 micro g/d was 65% for omalizumab and 40% for placebo; for those treated with < 800 micro g/d, the response rates were 63% and 55%, respectively). A low FEV(1) was also predictive (p = 0.072; response rates for those with FEV(1) <or= 65% predicted were 60% for omalizumab and 40% for placebo; for those with FEV(1) >or= 65% predicted, the response rates were 67% and 53%, respectively). Seventy-six percent of patients had at least one of these factors. This subgroup showed odds of being a responder (composite definition) 2.25 times higher (95% confidence interval, 1.68 to 3.01) than placebo. Some 38% of patients treated with omalizumab showed a response (composite definition) at the first evaluation time point at 4 weeks, increasing to 64% at week 16 (vs 48% for placebo; p < 0.001). Among omalizumab responders at 16 weeks, only 61% had responded at 4 weeks whereas 87% had responded at 12 weeks. Patients who benefit most when omalizumab is administered as add-on therapy are those receiving high doses of BDP, those with a history of frequent emergency asthma treatment, and those with poor lung function. Patients should be treated with omalizumab for a minimum duration of 12 weeks.

Sensitive liquid chromatographic/tandem mass spectrometric method for the determination of beclomethasone dipropionate and its metabolites in equine plasma and urine.

Beclomethasone dipropionate (BDP) is a potent pro-drug to beclomethasone (BOH) and is used in the treatment of chronic and acute respiratory disorders in the horse. The therapeutic dose of BDP (325 microg per horse) by inhalation results in very low plasma and urinary concentrations of BDP and its metabolites that pose a challenge to detection and confirmation by equine forensic laboratories. To solve this problem, a method involving the use of a liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) was developed for the detection, confirmation and quantification of the analytes in equine samples. Ammonium formate or acetate buffer added to LC mobile phase favored the formation of [M + H](+) ions from BDP and its metabolites, whereas formic acid led to the formation of sodium and potassium adduct ions ([M + Na](+), [M + K](+)) together with [M + H](+) ions. Acetonitrile, on the other hand, favored the formation of abundant solvent adduct ions [M + H + CH(3)CN](+) with the analytes under electrospray ionization (ESI) and atmospheric pressure chemical ionization conditions. In contrast, methanol formed much less solvent adduct ions than acetonitrile. The solvent adduct ions were thermally stable and could not be completely desolvated under the experimental conditions, but they were very fragile to collision-induced dissociation (CID). Interestingly, these solvent adduct ions were observed on a triple-quadrupole mass spectrometry but not on an ion trap instrument where helium used as a damping gas in the ion trap might cause the solvent adduct ions desolvated by collision. By CID studies on the [M + H](+) ions of BDP and its metabolites, their fragmentation paths were proposed. In equine plasma at ambient temperature over 2 h, BDP and B21P were hydrolyzed in part to B17P and BOH, respectively, but B17P was not hydrolyzed. Sodium fluoride added to equine plasma inhibited the hydrolysis of BDP and B21P. The matrix effect in ESI was evaluated in equine plasma and urine samples. The method involved the extraction of BDP and its metabolites from equine plasma and urine samples by methyl tert-butyl ether, resolution on a C(8) column with a mobile phase gradient consisting of methanol and ammonium formate (2 mmol l(-1), pH 3.4) and multiple reaction monitoring for the analytes on a triple-quadrupole mass spectrometer. The detection limit was 13 pg ml(-1) for BDP and B17P, 25 pg ml(-1) for BOH and 50 pg ml(-1) for B21P in plasma and 25 pg ml(-1) for BOH in urine. The method was successfully applied to the analysis of equine plasma and urine samples for the analytes following administration of BDP to horses by inhalation. B17P, the major and active metabolite of BDP, was detected and quantified in equine plasma up to 4 h post-administration by inhalation of a very low therapeutic dose (325 microg per horse) of BDP.

Initial Improvements in Lung Function and Bronchial Hyperresponsiveness Are Maintained During 5 Years of Treatment With Inhaled Beclomethasone Dipropionate and Terbutaline

Treatment with inhaled corticosteroids reduces bronchial hyperresponsiveness and relieves airways obstruction in patients with asthma. Up to now, it is unknown whether initial improvements are maintained over a long period of time. Therefore, we assessed whether initial improvements in FEV(1), provocative concentration of histamine causing a 20% fall in FEV(1) (PC(20)), and peak expiratory flow (PEF) persist with a constant dose of inhaled corticosteroids. Furthermore, we investigated whether FEV(1), PC(20), PEF indexes, and symptom scores improve after increasing the dose of inhaled corticosteroids in patients who did not respond sufficiently to treatment with beclomethasone dipropionate (BDP), 800 microg/d. Sixty-eight patients with bronchial hyperresponsiveness and airways obstruction completed a previous study on 3 years of treatment with terbutaline, 500 microg qid, and BDP, 200 microg qid. Fifty-eight of these patients participated in the current extension of another 2.5 years of follow-up. Every 6 months, FEV(1) and PC(20) were measured. Five patients dropped out of the study, one for pulmonary reasons. Forty-four patients continued treatment with BDP, 800 microg/d (BDP-800 group), and 9 patients received a higher dose of BDP (500 microg tid; BDP-1,500 group) after the first 3 years because of a rapid decline in FEV(1) (> 50 mL/yr) despite BDP treatment during the previous study period. After the initial improvement, the mean slope of individual regression lines for FEV(1), PC(20), and morning PEF were - 28 mL/yr, - 0.01 doubling concentrations per year, and 0.6 L/min/yr, respectively, in the BDP-800 group. In the BDP-1,500 group, there were no statistically significant improvements in FEV(1), PC(20), PEF indexes, and symptom scores after increasing the dose of BDP. We conclude that initial improvements in FEV(1), PC(20), and PEF are well preserved over 5 years in patients with obstructive airways diseases who are treated with terbutaline and BDP. In the patients who responded sufficiently to 800 microg/d of BDP, there was no accelerated decline in FEV(1) compared with the general population. Increasing the dose of BDP in a small group of patients with an accelerated fall in FEV(1) (initially treated with a moderate dose of BDP) resulted in no significant improvement in FEV(1), PC(20), PEF indexes, and symptom scores.