Step-down and step-up therapy in moderate persistent asthma

BACKGROUND: A step-down therapy may be more beneficial for the management of asthma than a step-up therapy. METHODS: Eighty-two asthmatic patients with moderate persistent asthma were enrolled in the study and randomized into three groups. One group of patients received 400 microg/day of beclomethasone dipropionate (BDP) for 4 weeks and then 800 microg/day for another 4 weeks (step-up group). The other two groups of patients received 1,200 microg/day of BDP for 4 weeks with or without short-term oral steroid (prednisolone, 0.5 mg/day for 1 week) and then 800 microg/day for another 4 weeks (step-down group). Severe exacerbation of asthma, asthma symptoms, respiratory function and rescue use of inhaled beta(2)-agonists were monitored. If asthma was well controlled, the dose of BDP was decreased every 3 months and if asthma was exacerbated, the dose of BDP was increased until 8 months after the initial treatment. RESULTS: Twenty-two patients during the run-in period, 4 patients in the step-up group, 2 patients in the step-down group treated with a high dose of BDP and no patients in the step-down group with oral steroids during first 4 weeks dropped out because of severe exacerbation of asthma. Although asthma symptoms and respiratory function significantly improved 8 weeks after the therapy in all groups, more significant and prompt improvements of these parameters were observed in patients of the step-down group than in patients of the step-up group after the first 2 weeks of treatment. Furthermore, step-down therapy with short-term oral steroid resulted in the lowest maintenance doses of BDP at 8 months of the three groups. CONCLUSIONS: These results suggest that step-down therapy starting with a high dose of inhaled steroid and short-term oral steroid is more effective in gaining prompt control of asthma and reducing the severe exacerbation of asthma and the maintenance dose of inhaled steroids than a step-up therapy starting with a low dose of inhaled steroids in patients with moderate persistent asthma.     

Effects of inhaled beclomethasone dipropionate on serum IgE levels and clinical symptoms in atopic asthma

BACKGROUND: A high serum immunoglobulin (Ig)E level is considered a potent predictor for the development of asthma and IgE is targeted for treatment of asthma. Although inhaled corticosteroids are well established in the treatment of asthma, the effects of inhaled corticosteroids on serum IgE levels in asthma remain uncertain. METHODS: We therefore examined asthma symptoms, concentrations of total serum IgE and specific IgE antibodies to selected allergens, blood eosinophil counts and lung functions before and 3 months after treatment with either inhaled beclomethasone dipropionate (BDP; 800 microg/day) (n = 7) or inhaled beta2-agonists alone (n = 7) in patients with atopic asthma in a randomized, double-blind, parallel-group controlled trial. RESULTS: Inhaled BDP significantly improved asthma symptom scores and forced expiratory volume in 1 s, and decreased blood eosinophil counts, total serum IgE levels and specific IgE antibodies to house dust mite and cedar. Decreases in total serum IgE significantly correlated with an improvement in asthma symptom scores. In contrast, none of parameters altered in patients with atopic asthma treated with inhaled beta2-agonists alone. CONCLUSIONS: Inhaled corticosteroids may improve the subsequent clinical course of atopic asthma in association with a reduction of serum IgE levels.     

A new spacer, Babyhaler, for BDP inhalation therapy in severe infantile asthma]

Recently, it has been recognized that airway inflammation is the most important pathogenesis of bronchial asthma, and inhaled corticosteroids therapy is effective for childhood asthma. However, using metered dose inhalers (MDI) of beclomethasone dipropionate (BDP) is difficult for infants. In this study, we administered BDP inhalation therapy with a new spacer, Babyhaler, for five cases of early childhood with severe infantile asthma that we could not control even by combination of theophylline round the clock (RTC) therapy and disodium cromoglycate (DSCG) + beta 2 stimulant (beta 2) regular use. We compared symptom score of asthma attack between the pre-treatment period (prior 2 weeks) and post-treatment period (following 8 weeks) of BDP inhalation therapy with Babyhaler. As a result, symptom score decreased significantly within 4 weeks after treatment of BDP with Babyhaler as compared with the score before treatment of BDP. These findings suggest that Babyhaler is useful for BDP inhalation therapy in infantile asthma.     

Long-term comparison of three combinations of albuterol, theophylline, and beclomethasone in children with chronic asthma.

Three combination regimens, (1) inhaled albuterol (ALB) with oral theophylline (THEO), (2) inhaled ALB with inhaled beclomethasone dipropionate (BDP), or (3) inhaled ALB, inhaled BDP, and oral THEO, were evaluated and compared as optimal pharmacotherapy for chronic asthma in 111 children. In this double-blind, parallel-group, multicenter study, children, aged 6 to 16 years with moderately severe asthma (unstable despite daily medications), were treated with one of the combinations for 12 weeks. Patients were evaluated every 4 weeks by spirometry and serum THEO measurement. Patients kept daily symptom diaries, measured peak flow rates twice daily, and recorded adverse events. Treatment groups did not differ in disease or demographic characteristics at study entry. All three combination treatments provided and maintained significant improvement in FVC, FEV1, and FEF25%-75% volume points, and compared with that of pretreatment, with no significant differences between treatments. Throughout the 12-week treatment period, however, patients receiving BDP had lower symptom scores, fewer had more than one asthma attack, fewer required "bursts" of prednisone (p = 0.001), and fewer required rescue medication (p = 0.009). Significantly more patients receiving BDP said that they felt better than they did at the beginning of the study compared with the number of patients not receiving BDP (p = 0.002). Adverse events were similar among treatment groups.     

Effects of pranlukast, a cysteinyl leukotriene receptor 1 antagonist, combined with inhaled beclomethasone in patients with moderate or severe asthma.

BACKGROUND: Although inhaled steroids are used as the first line of therapy in asthmatic patients, symptoms of asthma do not improve completely in some patients. OBJECTIVE: To investigate the effects of pranlukast, a cysteinyl leukotriene receptor 1 antagonist, in patients with moderate/severe asthma, when combined with beclomethasone dipropionate (BDP). METHODS: Protocol 1: After a 2-week observation period, 41 patients with moderate asthma were divided into those receiving BDP at 1,600 microg/day or 800 microg/day + pranlukast (450 mg/day). The effect of treatment was evaluated by measuring AM peak expiratory flow rate, symptom score, frequency of beta2-agonists, and daily variability of peak expiratory flow rate. Protocol 2: 39 patients participated in this study including those with moderate asthma on 800 microg/day BDP (group I), severe asthma on BDP at 1,600 microg/day (group II), and severe asthma on 1,600 microg/day BDP + 5 to 20 mg prednisolone (group III). Patients of all groups were additionally treated with pranlukast. RESULTS: Protocol 1: Both treatment regimens resulted in improvement in each clinical parameter. There were no significant differences in the effects of two treatment regimens. Protocol 2: Pranlukast was effective in group I and II, but not in group III. In groups I and II, pranlukast tended to be more effective when BDP was introduced within the first year of onset of asthma. CONCLUSIONS: Pranlukast is effective for patients with moderate asthma and those patients with severe asthma who are not treated with oral steroids. Pranlukast is more effective in patients treated with BDP early after onset.     

A six-month, placebo-controlled comparison of the safety and efficacy of salmeterol or beclomethasone for persistent asthma.

BACKGROUND: There is a paucity of data comparing the long-term safety and efficacy of long-acting inhaled beta2-agonists versus low-dose inhaled corticosteroids in the treatment of asthma. OBJECTIVE: To compare the safety and efficacy of salmeterol xinafoate, beclomethasone dipropionate (BDP), and placebo over a 6-month treatment period in patients with persistent asthma. METHODS: Salmeterol (42 microg twice daily), BDP (84 microg four times daily), or placebo was administered via metered-dose inhaler to 386 adolescent and adult inhaled corticosteroid-naive patients in a randomized, double-blind, double-dummy, parallel-group study. Eligible patients demonstrated a forced expiratory volume in 1 second (FEV1) from 65% to 90% of predicted values. Pulmonary function, symptom control, frequency of asthma exacerbations, bronchial hyperresponsiveness (BHR) to methacholine challenge, and adverse events were assessed. RESULTS: There were few statistically significant differences between the two active treatments over 6 months of therapy. Asthma symptoms and lung function were significantly improved with both salmeterol and BDP compared with placebo (changes from baseline in FEV1 of 0.28 L (SE = 0.04) and 0.23 L (SE = 0.04), respectively, compared with 0.08 L (SE = 0.04); P < or = .014). There were no significant differences among the treatment groups with respect to the distribution of asthma exacerbations over time. Both salmeterol and BDP significantly reduced BHR compared with placebo (P < or = .033; changes from baseline of 1.29 (SE = 0.26) and 1.42 (SE = 0.24) doubling doses at 6 months, respectively, compared with 0.24 (SE = 0.29) doubling dose for placebo). No rebound effect in BHR was seen upon cessation of any of the three treatment regimens. There were no clinically important differences in the safety profiles among the three treatments. CONCLUSIONS: Both salmeterol and BDP are effective and well-tolerated when administered for 6 months to inhaled corticosteroid-naive patients with persistent asthma.     

A comparison of the effects of nedocromil sodium and beclomethasone dipropionate on pulmonary function, symptoms, and bronchial responsiveness in patients with asthma

The efficacy of nedocromil sodium (NED) (4 mg twice daily) and beclomethasone dipropionate (BDP) (200 micrograms twice daily) in controlling the symptoms of asthma, the pulmonary function, and bronchial responsiveness to histamine was assessed in a double-blind, double-dummy, crossover study of 39 adult patients with chronic asthma. The patients, most of whom were assessed to be affected to a moderate degree, were insufficiently controlled in their current regimen of inhaled and/or oral bronchodilators. A 2-week baseline period preceded 6 weeks of treatment with each of the study drugs. Both treatment groups demonstrated improvements from baseline in clinical assessment of lung function performed after the first 6 weeks of treatment. No significant differences were observed when the effects of the treatments were compared on FEV1, FVC, and peak expiratory flow. Bronchial reactivity to histamine, measured as the amount of histamine causing a 20% fall in FEV1 (PC20), decreased significantly (p less than 0.05) after 6 weeks of treatment with BDP compared to the effect of NED treatment. Asthma severity, symptom score, and inhaled bronchodilator use demonstrated significantly better results with BDP. After crossover of treatment, the group transferring from NED to BDP continued to improve, whereas the group crossing from BDP to NED tended to demonstrate a major deterioration during the first 3 weeks, after which a stabilization or an increase in FEV1, FVC, and ln PC20 appeared to occur. It is concluded that NED for inhalation is a potent new drug for treatment of both atopic and nonatopic subjects with asthma. With the number of patients and dosages used, the effect on the pulmonary function was not significantly different from that of BDP after the initial 6 weeks of treatment, but BDP had a better effect on asthma severity, overall opinions, symptom score, bronchodilator use, ln PC20, and morning peak expiratory flow.     

Effect of inhaled indomethacin in asthmatic patients taking high doses of inhaled corticosteroids

Background: Cyclooxygenase products of arachidonic acid may play a part in bronchoconstriction and airway inflammation in asthma. Objective: We sought to determine the effect of inhaled indomethacin on asthma control and asthma exacerbations during reduction of inhaled corticosteroids in patients with moderate-to-severe steroid-dependent asthma. Methods: We conducted a double-blind, randomized, parallel-group, multicenter study in 38 patients with asthma taking high doses (≥1500 μg/d) of beclomethasone dipropionate (BDP). After a run-in period, patients were assigned inhaled indomethacin (50 mg/d) or placebo for 6 weeks, during which the daily doses of BDP were reduced to half at week 2 and then to one third of the baseline dose at week 4. Results: Data were available from 34 patients. After the reduction of BDP doses, FEV₁, peak expiratory flow, asthma symptoms, and exhaled nitric oxide concentrations deteriorated in both treatment groups, but these effects were less pronounced in the indomethacin group compared with the placebo group. During the 6-week treatment period, 89% of the patients receiving placebo had relapse of asthma, whereas only 38% of those receiving inhaled indomethacin did so (P = .003). Conclusion: Inhalation of indomethacin can reduce asthma exacerbations induced by reduction of high-dose inhaled corticosteroid in steroid-dependent asthma. (J Allergy Clin Immunol 2000;105:1134-9.)     

Comparison of roflumilast, an oral anti-inflammatory, with beclomethasone dipropionate in the treatment of persistent asthma

BACKGROUND: Roflumilast is an oral, once-daily phosphodiesterase 4 inhibitor with anti-inflammatory activity in development for the treatment of asthma. Roflumilast was compared with inhaled beclomethasone dipropionate (BDP) in patients with asthma. METHODS: In a double blind, double-dummy, randomized, noninferiority study, 499 patients (forced expiratory volume in 1 s [FEV1] = 50-85% predicted) received roflumilast 500 microg once daily or BDP 200 microg twice daily (400 microg/day) for 12 weeks. Lung function and adverse events were monitored. RESULTS: Roflumilast and BDP significantly improved FEV1 by 12% (270 +/- 30 ml) and 14% (320 +/- 30 ml), respectively (P < 0.0001 vs baseline). Roflumilast and BDP also significantly improved forced vital capacity (FVC) (P < 0.0001 vs baseline). There were no significant differences between roflumilast and BDP with regard to improvement in FEV1 and FVC. Roflumilast and BDP showed small improvements in median asthma symptom scores (-0.82 and -1.00, respectively) and reduced rescue medication use (-1.00 and -1.15 median puffs/day, respectively; P < 0.0001 vs baseline). These small differences between roflumilast and BDP were not considered clinically relevant. Both agents were well tolerated. CONCLUSIONS: Once daily, oral roflumilast 500 microg was comparable with inhaled twice-daily BDP (400 microg/day) in improving pulmonary function and asthma symptoms, and reducing rescue medication use in patients with asthma.     

Mometasone furoate: efficacy and safety in moderate asthma compared with beclomethasone dipropionate.

BACKGROUND: Mometasone furoate (MF) is a new inhaled glucocorticoid administered by dry powder inhaler (DPI). OBJECTIVE: MF-DPI was evaluated for safety and efficacy and compared with placebo DPI and beclomethasone dipropionate (BDP) administered by metered dose inhaler (MDI) in the treatment of patients with moderate persistent asthma. METHODS: Eligible patients (n = 227), 13 to 75 years of age, maintained on inhaled glucocorticoids before entering the trial, were randomized to receive: MF-DPI, 100 microg, twice daily, MF-DPI, 200 microg, twice daily, BDP MDI, 168 microg, twice daily, or placebo in a 12-week, multicenter, double-blind study. RESULTS: At endpoint, FEV1 (primary efficacy variable) significantly improved for all three active treatments compared with placebo (P < .01, all comparisons). The response to MF-DPI, 200 microg, twice daily treatment was approximately twice as large as the response to MF-DPI, 100 microg, twice daily or BDP MDI treatment, although the differences between these groups did not reach statistical significance. Secondary efficacy variables including PEFR, asthma symptoms, nocturnal awakenings, and albuterol use showed similar trends. The MF-DPI, 100 microg, twice daily and BDP MDI, 168 microg, twice daily treatment groups produced comparable results for all efficacy variables. CONCLUSIONS: MF-DPI, 100 microg and 200 microg, twice daily were well-tolerated and significantly improved lung function and symptom control in the treatment of patients with moderate persistent asthma. In this study, MF-DPI, 200 microg, twice daily seemed to be the most effective dosage.     

A double-blind placebo-controlled study of the effect of inhaled beclomethasone dipropionate for 2 years in patients with nonasthmatic chronic obstructive pulmonary disease

Treatment of chronic obstructive pulmonary disease (COPD) with inhaled and oral corticosteroids is common, although their exact role is unclear. Previous studies suggest these drugs may reduce decline in lung function in this group of patients. We report a study investigating the effect of inhaled beclomethasone diproprionate (BDP) on lung function and symptoms in a group of patients with COPD. Treatment was given for 2 years, and the decline in FEV₁ in individual patients calculated over this period. Ninety-eight patients were randomized for the study, 59 completing 2 years of treatment. Patients withdrawn had more severe airflow obstruction. Decline in FEV₁, measured both prior to and after bronchodilator, was less in patients receiving inhaled BDP, although the differences failed to reach statistical significance except in a subgroup of patients with more severe airflow obstruction. Exacerbation rates were also reduced by inhaled BDP, but again the differences failed to reach conventional levels of statistical significance. The results of this study are consistent with previous published work, but further insight into the long-term role of corticosteroids in COPD await the publication of large studies which have recently been completed. Although the changes seen in this study and others are numerically small, the rate of decline in FEV₁ returned to normal levels expected from age-related decline, and hence such treatment combined with other strategies may well have a significant role in the long-term treatment of this condition.     

Comparison of dose-response effects of inhaled beclomethasone dipropionate and budesonide in the management of asthma

The dose-response effects of inhaled beclomethasone dipropionate (BDP) and budesonide (BUD) administered b.i.d. with the aid of metered dose aerosols were studied in 128 patients (67 men and 61 women, mean age 53 years) suffering from asthma bronchiale. The study was designed as a multi-centre, double-blind, four-period cross-over study, followed by a single-blind double placebo period. BDP was administered in doses of 400 and 1000 micrograms, and BUD in doses of 400 and 800 micrograms. The results in terms of peak expiratory flow (PEF) in the morning and evening, daily symptoms score and use of inhaled beta 2-agonists did not reveal any clinically significant differences between the drugs or between high (800 micrograms BUD, 1000 micrograms BDP) and low (400 micrograms BUD/BDP) doses. However, statistically significant differences were recorded for the corresponding parameters when comparing the placebo with preceding steroid periods. Adverse effects consisting mainly of oropharyngeal candidiasis, hoarseness and cough occurred in 54 of 468 treatment months (12%). The carry-over effects of inhaled steroids are longer lasting than was previously assumed.     

Anti-proliferative and anti-remodelling effect of beclomethasone dipropionate, formoterol and salbutamol alone or in combination in primary human bronchial fibroblasts

Background:  Bronchial asthma is characterized by lower airway inflammation and remodelling. Anti-inflammatory treatment with inhaled corticosteroids (ICS) provides the mainstay of asthma therapy together with bronchodilation induced by short- and long-acting inhaled β₂-agonists. Lower airway fibroblasts may play a critical role in airway inflammation and remodelling, suggesting that they might represent an important target for the major anti-asthmatic drugs. The aim of our study was to investigate the effects of beclomethasone dipropionate (BDP), salbutamol and formoterol either alone or in combination on in vitro cultures of human bronchial fibroblasts.
Methods:  Fibroblasts were cultured in the presence of pro-inflammatory and proliferative stimuli, BDP, salbutamol and formoterol. The effects of drugs on cell proliferation were ascertained by ³H-thymidine incorporation. CD90 and CD44 expression were detected by flow cytometry and fibronectin secretion using the enzyme-linked immunosorbent assay technique.
Results:  This study showed that BDP alone has significant anti-proliferative effects on lung fibroblasts treated with basic fibroblast growth factor and the combination of BDP with formoterol or salbutamol strengthen these effects. Short-acting β₂-agonist (SABA) or long-acting β₂-agonist (LABA) by themselves did not show any significant effect on the different cultures. CD44 and CD90 expression and fibronectin production were modulated by pro-inflammatory and proliferative stimuli; the addition of the drugs brought them back near to the basal level.
Conclusions:  From this in vitro study, we can conclude that BDP, when combined with salbutamol or formoterol, exhibits enhanced anti-remodelling activity in bronchial fibroblasts, providing new insights on the additive effects of ICS and SABAs and LABAs for asthma therapy.     

Usefulness of patient education and quality of life (QOL) evaluation in asthma patients]

Achieving successful treatment of bronchial asthma depends on its control by the patient. We implemented a program of educating asthma patients and conducted a QOL survey to objectively evaluate the patients'conditions. Thirty-nine asthma patients who were receiving treatment with an inhaled corticosteroid [beclomethasone dipropionate (BDP) ] on an outpatient basis at our hospital, received instructions on proper drug administration in cooperation with the Pharmacy department of our hospital. The QOL survey (SF-36 and Marks et al. AQLQ) was conducted at the initial education session and again two months later. Thirty-two patients (82.0%) responded that they would like to continue to receive instructions on the administration of drugs. Significant improvements in Social, Concerns, Marks, and Scales were observed after the education. In addition, even those patients who stated that they did not want to receive instructions showed significant improvements in their QOL scores. The usefulness of patient education can be assessed by the change in the patients' QOL scores.     

An evaluation of the acceptance of budesonide turbuhaler by older Japanese patients with bronchial asthma when changed from fluticasone propionate (FP) or beclomethasone dipropionate (BDP)]

Although the clinical reputation of the inhaled steroid budesonide(R) (BUD) has become well established in Europe and the USA, we found that in clinical practice many older Japanese patients were resistant to changing to this form of inhaled steroid from fluticasone propionate (FP) or beclomethasone dipropionate (BDP). This study was accordingly designed to evaluate the acceptability and clinical efficacy of budesonide in older Japanese patients with bronchial asthma. METHODS: Forty-five Japanese asthma patients aged over 65 (22 using FP and 23 using BDP) were changed to BUD inhalation from their existing inhaled steroid. After two weeks, patients were questioned as to their acceptance of BUD, their inhalation technique was checked, and the duration of inhalation required to dispense the drug and peak expiratory flow (PEF) was measured. The rate of pharyngeal candidiasis was also assessed, both before and after changing to BUD. RESULTS: Most of the patients in both groups considered BUD inhalation to be easy and could quickly learn to use the Turbuhaler. However, as no sensation of drug inhalation was generally experienced, over 70% of patients felt anxious about whether they had successfully inhaled the medication. Furthermore, there were various misunderstandings in correct inhaler technique. Although there were no significant differences in PEF or in the rate of pharyngeal candidiasis before and after changing to BUD administration, side effects occurred in about 40% of both groups. In patients aged 65-74, 50.0% of patients who had previously been taking FP and 38.9% of those who had previously been taking BDP intended to continue BUD inhalation, while in patients over 75, only 8.3% of former users of FP and 20.0% of former users of BDP intended to continue using BUD. CONCLUSION: In older patients, factors influencing satisfaction with inhaled medication include not only ease of use and time needed to become accustomed to a new delivery method, but also the important issue of satisfaction with the sensation of drug inhalation.     

The prevalence and evolution of anemia associated with tuberculosis

Tuberculosis (TB) may produce abnormalities in the peripheral blood, including anemia. However, the evolution of TB-associated anemia with short-term combination anti-TB chemotherapy has not been well elucidated. The aim of this study was to characterize TB-associated anemia by clarifying its prevalence, characteristics, and evolution, through involving large numbers of patients with TB. The medical records of adult patients with TB diagnosed between June 2000 and May 2001 were reviewed. Among 880 patients with TB, 281 (31.9%) had anemia on diagnosis of TB, however, the hemoglobin concentration was less than 10 g/dL in only 45 patients (5.0%). Anemia was more frequently associated with the female and old age. Good treatment response, young age (< or =65 yr-old) and initial high hemoglobin were the predictive factor for resolution of anemia. In 202 patients with anemia (71.9%), anemia was normocytic and normochromic. During or after anti-TB treatment, anemia was resolved in 175 (64.6%) out of 271 patients without iron intake. The mean duration of resolution from the initiation of anti-TB treatment was 118.8+/-113.2 days. In conclusion, anemia is a common hematological abnormality in patients with TB and close observation is sufficient for patients with TB-associated anemia, because TB-associated anemia is usually mild and resolves with anti-TB treatment.     

Efficacy response of inhaled beclomethasone dipropionate in asthma is proportional to dose and is improved by formulation with a new propellant

BACKGROUND: This study tested the hypothesis that there would be improved asthma control with increasing doses of beclomethasone dipropionate (BDP) formulated in hydrofluoroalkane-134a (HFA-BDP) and the standard chlorofluorocarbon propellants (CFC-BDP). Because HFA-BDP has improved lung deposition compared with CFC-BDP, this study also tested the hypothesis that HFA-BDP would provide more effective control of asthma than CFC-BDP. METHODS: In this multicenter, randomized, parallel-group blinded study, asthmatic subjects who had deterioration in asthma control after discontinuation of inhaled corticosteroids were randomized to receive one of 6 possible treatments: 100 microg/d, 400 microg/d, or 800 microg/d of HFA-BDP or 100 microg/d, 400 microg/d, or 800 microg/d of CFC-BDP for 6 weeks. Changes in spirometry, daytime asthma symptom and nighttime asthma-related sleep disturbance scores, morning and evening peak expiratory flows, and daily use of inhaled beta-agonist for symptom control on diary cards were assessed over 6 weeks of treatment. RESULTS: Three hundred twenty-three patients were randomized to the 6 treatment groups, which had similar demographics and baseline lung function. There were significantly larger changes from baseline at week 6 in FEV(1) percent predicted with increasing doses of both HFA-BDP and CFC-BDP. The FEV(1) percent predicted dose-response curve for HFA-BDP was shifted to the left compared with the dose-response curve for CFC-BDP. By using the Finney bioassay method, it was calculated that 2.6 times as much CFC-BDP would be required to achieve the same improvement in FEV(1) percent predicted as HFA-BDP (95% confidence interval, 1.1-11.6). All treatment groups except the 100 microg/d CFC-BDP group tolerated study drug well. Ten (17%) of 59 patients in this group reported an acute asthma episode, increased asthma symptoms (6 of the 8 reports of increased asthma symptoms were classified as severe), or both, and 8 patients withdrew from the study (3 for adverse events related to asthma). CONCLUSIONS: Increasing doses of inhaled corticosteroids lead to improved lung function and asthma control. Moreover, the reformulation of BDP in HFA enables effective asthma control at much lower doses than CFC-BDP.     

吸入糖皮质激素对哮喘儿童细胞免疫功能的影响

为了解糖皮质激素对免疫功能的作用，检测了哮喘发作期患儿。对经丙酸倍氯松（ＢＤＰ）吸入治疗的患儿及正常儿童外周血淋巴细胞膜ＩＬ－２受体（ｍＩＬ－２Ｒ）、超微结构、血浆游离ＩＬ－２受体（ｓＩＬ－２Ｒ）、淋巴细胞亚群及ＢＤＰ对体外培养淋巴细胞ｍＩＬ－２Ｒ的表达进行比较。结果显示，ＢＤＰ可以明显抑制ＰＨＡ刺激引起的体外培养淋巴细胞ｍＩＬ－２Ｒ的表达，引起淋巴细胞的凋亡，而吸入ＢＤＰ（２００μｇ／ｄ）的哮喘患儿（缓解期）除ｓＩＬ－２Ｒ比哮喘发作期显著降低（Ｐ＜０．０５）外，外周血淋巴细胞ｍＩＬ－２Ｒ及淋巴细胞亚群并未出现显著变化．结果提示，抑制淋巴细胞ｍＩＬ－２Ｒ表达和淋巴细胞活化可能是ＢＤＰ治疗哮喘等变态反应的重要机制之一。吸入ＢＤＰ主要是呼吸道局部作用，对全身细胞免疫指标影响不大     

Analysis of induced sputum before and after withdrawal of treatment with inhaled corticosteroids in asthmatic patients

To assess whether sputum eosinophilia predicts the recurrence of asthma symptoms after withdrawal of therapy in moderate stable asthmatics on low-dose inhaled corticosteroids. Randomized, double-blind, placebo-controlled study involving 30 subjects with stable asthma, asymptomatic, with low PEF variability measured over two run-in weeks, on treatment with low-dose inhaled beclomethasone dipropionate (BDP, 250 microgram b.i.d. in the last 3 months). At the end of the run-in, all patients underwent a methacholine challenge test and sputum induction (T1). They then stopped therapy and received either placebo (20 subjects, study group) or BDP at the same dose as in the previous 3 months (10 subjects, control group). They continued to monitor PEF and symptom score for 3 months, or until asthma symptoms recurred (diurnal and nocturnal symptom score >/=2 on two consecutive days). At the end of the study (T2), i.e., either within 5 days from the beginning of asthma symptoms or after 3 months in subjects without recurrence of asthma symptoms, all subjects repeated the methacholine challenge test and sputum induction. In the placebo-treated group, sputum eosinophils at T1 were significantly higher in subjects who subsequently developed recurrence of asthma symptoms (n = 7) after cessation of treatment than in subjects who remained asymptomatic for 3 months (8.2% [0-56.6] vs 0.9% [0-11], P < 0.05). At the time of recurrence of asthma symptoms, sputum eosinophil percentages significantly increased (from 8.2% [0-56.6] to 16.6% [5.8-73.6], P < 0.05). The positive predictive value of sputum eosinophils for the recurrence of asthma symptoms was 71%, while the negative predicting value was 84%. In the BDP-treated control group, none of the subjects experienced recurrence of asthma symptoms, and sputum eosinophil percentages measured at the beginning (T1) and at the end (T2) of the study were similar. Sputum eosinophil percentages may vary over a wide range in asthmatic subjects, although regularly treated and apparently well controlled. However, high sputum eosinophil percentages are related to early recurrence of asthma symptoms after cessation of inhaled corticosteroids.