Efficacy and Safety of Budesonide Inhalation Powder (Pulmicort Turbuhaler®) During 52 Weeks of Treatment in Adults and Children with Persistent Asthma

Background. Inhaled corticosteroids are the agents of choice for treating persistent asthma. Objective. To evaluate the long-term efficacy and safety of budesonide inhalation powder (Pulmicort Turbuhaler®) in patients with mild to severe persistent asthma. Methods. Patients (n = 1133) received open-label budesonide (dose range, 100-800 µg b.i.d.) for 52 weeks following 2 weeks to 5 months of treatment in one of four double-blind, placebo-controlled studies. Patients, identified before the double-blind studies, included adults (n = 249) not receiving corticosteroids, adults (n = 384) and children (n = 356) previously maintained on inhaled corticosteroids, and adults (n = 144) previously maintained on oral corticosteroids. Results. Mean forced expiratory volume in 1 sec was 68.2% of predicted normal (n = 1133) at baseline (mean from two visits before randomization), 74.4% (n = 1132) at the end of double-blind treatment, 81.3% (n = 971) at week 52, and 80.1% (n = 1125) at last observation (including patients who discontinued early). Sixty-four patients maintained on oral corticosteroids before double-blind treatment entered the open-label study off oral corticosteroids, 58 of whom (91%) remained oral corticosteroid-free throughout the study. There was no evidence of basal or cosyntropin-stimulated hypothalamic-pituitary-adrenal axis function suppression, and the most commonly occurring adverse events were respiratory infection, sinusitis, and pharyngitis. Conclusions. During this 52-week, open-label study, budesonide maintained the improved pulmonary function and decreased oral corticosteroid use observed during previous double-blind treatment and was well tolerated, supporting its long-term use in adults and children with mild to severe persistent asthma.     

Once-Daily Administration of Budesonide Turbuhaler® was as Effective as Twice-Daily Treatment in Patients with Mild to Moderate Persistent Asthma

In a double-blind, randomized, placebo-controlled trial, 288 patients with mild to moderate persistent asthma currently on inhaled glucocorticosteroids (GCSs) were treated with budesonide Turbuhaler®, 200 µg once every night (q.n.), 100 µg twice-daily (b.i.d.), or placebo b.i.d. After 12 weeks, morning peak expiratory flow (PEF) increased in both groups treated with budesonide but decreased in placebo-treated patients. Symptom scores and bronchodilator use were significantly reduced in both groups receiving active treatment (p = 0.023-0.0001) compared with patients treated with placebo. There was no significant difference in outcome measurements between the two budesonide regimens. Thus, patients with mild to moderate persistent asthma receiving b.i.d. treatment with inhaled GCSs can usually be switched to budesonide Turbuhaler®, 200 µg, q.n. without loss of asthma control.     

Which factors predict success after discontinuation of inhaled budesonide therapy in children with asthma?

Urinary eosinophil protein X (UEPX) concentration, lung function, and nonspecific bronchial hyperreactivity were determined in 40 asthmatic children (asymptomatic for 6.4 +/- 3.0 months) (mean age 9.8 +/- 2.9 years) receiving inhaled budesonide, in order to establish whether measurement of these parameters is useful in determining discontinuation of inhaled corticosteroid therapy. After the discontinuation of therapy, patients were asked to come to the Outpatient Clinic if symptoms recurred and did not respond to beta2 mimetic usage in 24 hr. Otherwise they were to be seen 2-3 months later for a follow-up visit. UEPX concentration was determined and spirometry was performed on this visit. While UEPX concentrations had increased (p < 0.0001), FEV1, FEF 25-75 and PEF had decreased significantly 2.3 +/- 0.53 months after the cessation of inhaled budesonide therapy in all children (p = 0.004, p = 0.02, p = 0.02, respectively). Due to clinical deterioration, inhaled corticosteroid therapy had to be restarted in 19 (48%) of the children (Group I), while the remaining 21 (52%) (Group II) continued to be asymptomatic during the 2.3 +/- 0.5 months follow-up period. Although the initial UEPX concentrations, spirometer variables, and methacholine PC20 values of these two groups were not statistically different, the duration of clinical remission before discontinuation of budesonide prophylaxis was significantly longer in group II (p = 0.0037). We concluded that, in determining discontinuation of inhaled corticosteroid prophylaxis, duration of clinical remission seems to be a more useful criterion than measurement of UEPX levels, lung function test, and assessment of bronchial hyperreactivity.     

Effect of High Starting Dose of Budesonide Inhalation Suspension on Serum Cortisol Concentration in Young Children with Recurrent Wheezing Episodes

Introduction. There are no available data on the safety of recommended schedules for the initiation of treatment with budesonide inhalation suspension in children with recurrent wheezing episodes. We compared the safety of high and low starting dose of budesonide by measuring their effect on plasma cortisol concentration. Methods. A randomized double-blind, placebo-controlled design was used. Twenty-nine children ages 6 months to 3 years were divided into three groups: (1) high starting dose: 1 mg budesonide inhalation suspension twice daily followed by a stepwise decrease of 25% every second day for 8 days (n = 11); (2) low starting dose: 0.25 mg twice daily for 8 days (n = 11); (3) placebo (n = 7). The 8 AM (fasting) and 1-hour post-ACTH stimulation plasma cortisol concentrations were measured before and 10 days after initiation of budesonide treatment. Results. Before treatment and after 8-10 days of treatment, there was no significant difference in mean serum cortisol concentration in the high starting dose, low-dose and placebo groups, either at 8 AM or at 1 hour after ACTH stimulation. Conclusion. The administration of nebulized suspension of budesonide at a high starting dose (2 mg/day for 2 days) followed by a rapid stepwise decrease over 8 days was safe, causing similar changes in serum cortisol levels to low-dose budesonide suspension or placebo.     

The Effects of Asthma on Dental and Facial Deformities

Objective. The purpose of the study was to observe facial and teeth alterations in adult patients with asthma as opposed to a group who suffered from hypertension.    Methods. All patients included in this cross-sectional observational study were interviewed to obtain clinical data. Patients also followed an orthodontic assessment using model-facial photographic and gypsum casts to diagnose malocclusion and dentofacial deformities. Asthmatic patients were divided in two groups according to asthma onset under or over 14 years of age.    Results. A total of 61 asthmatics and 53 hypertensive patients were evaluated. Dental midline symmetry was significantly lower in asthmatics than in the hypertensive group (p = 0.006), whereas incompetent lip posture and open nasal lip angle were significantly more frequent in the asthmatic group than in the control group (p = 0.007 and 0.016, respectively). Asthmatics had more dental crossbite (p = 0.004), overbite (p = 0.01), overjet (p = 0.01), smaller inter bicuspids distance (p = 0.0009) and inter molar distance (p = 0.0001) than the control group. More crowding than diastems was observed in asthmatic patients. An association between the crossbite (p = 0.02) and maxillary crowding (p = 0.03) was also observed with the earlier age of asthma onset. Conclusion: The findings of this study lead us to note that dentofacial anomalies are related to asthma.     

Peripheral Inflammation in Patients with Asthmatic Symptoms but Normal Lung Function

Some patients with asthmatic symptoms and eosinophilic airway inflammation have normal lung function and thus do not meet the current diagnostic criteria of asthma. Exhaled nitric oxide (NO) measurement at multiple exhalation flow rates can be used to assess alveolar and bronchial NO output and inflammation. We tested whether alveolar or bronchial NO output is increased in subjects having asthmatic symptoms but normal lung function. Exhaled NO concentration was measured at three exhalation flow rates (100, 175, and 370 mL/s) to assess alveolar NO concentration and bronchial NO flux in 23 patients with asthmatic symptoms but normal lung function (“asthmatic symptoms group”), 40 patients with asthma, and 40 healthy control subjects. The asthmatic symptoms group had increased bronchial NO flux (1.7 ± 0.3 nL/s, p = 0.016) and alveolar NO concentration (1.8 ± 0.2 parts per billiant (ppb), p = 0.010) compared with healthy controls (0.7 ± 0.1 nL/s and 1.0 ± 0.1 ppb, respectively). Patients with asthma had even higher bronchial NO flux (2.5 ± 0.3 nL/s, p = 0.024) but normal alveolar NO concentration (1.1 ± 0.2 ppb, p = 0.664). In asthmatic symptoms group, alveolar NO concentration correlated positively with blood eosinophil count and negatively with small airway function (FEF_50% and FEF_75%). In conclusion, patients with asthmatic symptoms but normal lung function have increased alveolar NO concentration and mildly elevated bronchial NO flux suggesting a more peripheral inflammation than in patients with asthma.     

Bone mineral density and bone metabolism of prepubertal children with asthma after long-term treatment with inhaled corticosteroids

Little is known about the effect of long-term treatment with inhaled corticosteroids (ICS) on bone mineral density (BMD) in asthmatic children. In the present cross-sectional study BMD, bone metabolism, height, body composition, and bone age were evaluated in 40 prepubertal children (21 boys) with asthma, treated with a moderate to high dose of ICS over a period of 3 to 8 years. Body composition and BMD of the lumbar spine and total body were measured by Dual Energy X-ray Absorptiometry. BMD results were compared with 148 prepubertal healthy children of the same population. Blood samples were taken for the determination of biochemical bone parameters. The asthmatic children had decreased height, lean tissue mass and fat mass, and a delay of bone maturation, indicating growth retardation. ICS-treated asthma was negatively correlated with total body BMD in a multiple regression model with adjustment for age, gender, height and weight (P = 0.01). Duration of ICS therapy correlated negatively with total body BMD when it was added to the model (P = 0.01). Lumbar spine BMD was not affected by ICS in children with ICS-treated asthma. If age of the asthmatic children was replaced by their bone age in the model, no significant correlation was found between ICS-treated asthma and total body or lumbar spine BMD. The biochemical parameters of bone metabolism were within normal limits. In conclusion, children with asthma who have used ICS daily for 3 to 8 years had lower total body BMD than healthy controls. Long-term longitudinal studies are needed to investigate whether these children attain a normal peak bone mass. Pediatr. Pulmonol. 1997; 24:379–384. © 1997 Wiley-Liss, Inc.     

Once‐Daily Inhaled Budesonide for the Treatment of Asthma: Clinical Evidence and Pharmacokinetic Explanation

Background. Budesonide, a widely used inhaled corticosteroid (ICS) with a favorable therapeutic ratio, is available via a dry powder inhaler (Pulmicort Turbuhaler®) and as a suspension for nebulization (Pulmicort Respules®). Methods. MEDLINE and an AstraZeneca database were searched to identify relevant controlled clinical trials published between 1986 and 2002 using the key words budesonide OR inhaled corticosteroid, AND once daily. Results. Thirty‐four controlled clinical studies involving once‐daily administration of budesonide to asthmatic patients were identified. Excluding long‐term studies, this review presents data from 23 controlled studies for 4466 adults or adolescents and 1532 children with asthma and demonstrates efficacy of budesonide in both corticosteroid‐naïve patients and patients previously treated with ICS. Once‐daily administration of budesonide achieves clinical efficacy comparable with that of twice‐daily regimens in patients with mild‐to‐moderate asthma and is equally effective when given in the morning or evening. Once‐daily administration simplifies treatment regimens and may improve patient compliance. The tolerability profiles of budesonide once‐daily via Turbuhaler® or as budesonide inhalation suspension are good and comparable with those for twice‐daily dosing. Conclusions. Once‐daily budesonide is effective and well tolerated as initial treatment for adults and children with mild asthma and as maintenance therapy in patients with more severe asthma once asthma control has been achieved.     

Effects of inhaled corticosteroid and short courses of oral corticosteroids on bone mineral density in asthmatic patients : a 4-year longitudinal study.

BACKGROUND: It is not certain whether inhaled corticosteroid (ICS) therapy reduces bone mineral density (BMD) in asthmatic patients. In addition, the potential risk of osteoporosis associated with the rescue use of short courses of oral corticosteroids (SC-OCS) is unclear. OBJECTIVE: To evaluate the effect of inhaled beclomethasone dipropionate (BDP) and SC-OCS on BMD in asthmatic patients. DESIGN: A 4-year longitudinal study. METHOD: Lumbar BMD was measured twice by dual-energy x-ray absorptiometry at a mean (+/- SD) interval of 4.2 +/- 0.1 years in 35 asthmatic adults (15 men and 20 postmenopausal women; mean age at the second evaluation, 60.6 +/- 11.5 years) who had been treated with BDP and SC-OCS. RESULTS: The average period of BDP treatment was 7.7 +/- 2.2 years (range, 4.8 to 13.0 years) at the second evaluation. During the study period, the daily dose of BDP was 765 +/- 389 microg (range, 100 to 1,730 microg), and the frequency of SC-OCS was 1.9 +/- 2.7 courses per year (range, 0.0 to 8.9 courses per year). As a whole, lumbar BMD was unchanged during the course of the study, whereas the Z score (ie, the percentage of normal value predicted from age and sex) increased significantly. Changes in BMD and Z scores in patients receiving high doses of BDP (ie, > 1,000 microg/d; n = 9) were not significantly different from those of patients receiving lower doses (ie, 2.5 courses per year; n = 9) showed a significantly greater loss in BMD and Z score compared with those receiving sporadic courses (ie, 相似文献   

Effect of inhaled steroids on lung function in young children: a cohort study.

The objectives of the present study were to determine the use of inhaled corticosteroids (ICS) for treating recurrent bronchial obstruction (rBO) in young children up to 2 yrs of age and to assess possible modifying effects of ICS on lung function in young children with rBO. From an observational, noninterventional birth cohort of 3,754 newborn children (3,697 with complete questionnaire data by 2 yrs of age), 306 children with documented rBO by age 2 yrs (cases) were identified along with 306 matched controls. Two tidal flow/volume measurements were taken, one at presentation of disease (children were steroid naive) and one at 2 yrs of age (mean age 11.2 and 25.6 months, respectively), from: 21 cases who subsequently received ICS (ICS+); 33 who did not (ICS-); and in 15 controls. The mean +/- SD duration of ICS treatment was 10.3 +/- 6.5 months. The main outcomes were treatment with ICS and baseline ratio of time to peak expiratory flow/total expiratory time (tPTEF/tE). From the entire cohort, 77 children (2.1%) and 21% of children with rBO had received ICS by 2 yrs of age. Baseline tPTEF/tE was significantly lower at the first visit only in ICS+ as compared to ICS- subjects, as well as in ICS+ and ICS- as compared to controls. The mean difference in baseline tPTEF/tE from first to second visit was borderline statistically significant in the ICS+ group only and correlated significantly with duration of ICS treatment. The present observational cohort study demonstrated that one-fifth of young children with recurrent bronchial obstruction had received inhaled corticosteroids. Early inhaled corticosteroid treatment improved lung function by age 2 yrs, mostly in those with the longest duration of treatment.     

Once-daily inhaled budesonide for the treatment of asthma: clinical evidence and pharmacokinetic explanation.

BACKGROUND: Budesonide, a widely used inhaled corticosteroid (ICS) with a favorable therapeutic ratio, is available via a dry powder inhaler (Pulmicort Turbuhaler) and as a suspension for nebulization (Pulmicort Respules). METHODS: MEDLINE and an AstraZeneca database were searched to identify relevant controlled clinical trials published between 1986 and 2002 using the key words budesonide OR inhaled corticosteroid, AND once daily. RESULTS: Thirty-four controlled clinical studies involving once-daily administration of budesonide to asthmatic patients were identified. Excluding long-term studies, this review presents data from 23 controlled studies for 4466 adults or adolescents and 1532 children with asthma and demonstrates efficacy of budesonide in both corticosteroid-na?ve patients and patients previously treated with ICS. Once-daily administration of budesonide achieves clinical efficacy comparable with that of twice-daily regimens in patients with mild-to-moderate asthma and is equally effective when given in the morning or evening. Once-daily administration simplifies treatment regimens and may improve patient compliance. The tolerability profiles of budesonide once-daily via Turbuhaler or as budesonide inhalation suspension are good and comparable with those for twice-daily dosing. CONCLUSIONS: Once-daily budesonide is effective and well tolerated as initial treatment for adults and children with mild asthma and as maintenance therapy in patients with more severe asthma once asthma control has been achieved.     

The prognosis for type 2 diabetic patients with heart disease. A 10-year observation study of 385 patients

The objective was to study the development and progression of heart disease in type 2 diabetic patients and to evaluate the influence of revascularisation procedures on its outcome. A 10-year observation study in 385 patients attending a hospital-based outpatient clinic was performed. A total of 156/385 patients developed myocardial infarction (n=68), angina (n=44), heart failure (n=34) or died (n=109). A high mortality was seen in patients with myocardial infarction (73%) and heart failure (71%), in contrast, to patients with angina (25%). Thirty patients had a coronary angiography because of angina, out of which 23 were revascularised. Four (17%) of patients with bypass surgery or angioplasty died compared with 57 (67%) of the patients with no intervention (p<0.001). The occurrence of myocardial infarction was associated with age (p<0.0001), and mean systolic (p<0.05) and diastolic (p<0.05) blood pressure and degree of albuminuria at entry (p<0.05). Heart failure was associated with age (p<0.0001), and mean HbA_1c levels (p<0.05), while angina was associated with age only (p<0.05). Death was associated with age (p<0.0001), diabetes duration (p<0.05), mean diastolic blood pressure (p<0.05), and degree of albuminuria at entry (p<0.0001). This study shows a high incidence of heart disease in patients with type 2 diabetes. The prognosis was better in patients who had had a revascularisation procedure. Thus, a more active attitude towards revascularisation may potentially improve the prognosis for type 2 diabetic patients with atherosclerotic heart disease.     

Budesonide/formoterol in a single inhaler for maintenance and relief in mild-to-moderate asthma: a randomized, double-blind trial

STUDY OBJECTIVE: To compare a novel asthma management strategy--budesonide/formoterol in a single inhaler for both maintenance therapy and symptom relief--with a higher dose of budesonide plus as-needed terbutaline. METHODS: This was a 6-month, randomized, double-blind, parallel-group study in patients with mild-to-moderate asthma (n = 697; mean age, 38 years [range, 11 to 79 years]; mean baseline FEV1, 75% of predicted; mean inhaled corticosteroid [ICS] dosage, 348 microg/d). Following a 2-week run-in period, all patients received two blinded, dry powder inhalers, one containing maintenance medication and one containing medication to be used as needed for the relief of symptoms. Patients were randomized to receive either budesonide/formoterol (80 microg/4.5 microg, two inhalations qd) for maintenance plus additional inhalations as needed for symptom relief, or budesonide (160 microg, two inhalations qd) for maintenance medication plus terbutaline (0.4 mg) as needed. The primary efficacy variable was morning peak expiratory flow (PEF). RESULTS: Patients receiving budesonide/formoterol showed greater improvements in morning PEF than patients receiving budesonide (increases of 34.5 L/min vs 9.5 L/min, respectively; p < 0.001). The risk of having a severe exacerbation (hospitalization/emergency department [ED] treatment, oral steroids for asthma, or a > or = 30% decrease from baseline in morning PEF on 2 consecutive days) was 54% lower with budesonide/formoterol vs budesonide (p = 0.0011). Budesonide/formoterol patients experienced 90% fewer hospitalizations/ED treatments due to asthma than budesonide patients (1 vs 10, respectively; p = 0.026). The increased efficacy with budesonide/formoterol was achieved with less ICS than was used in the budesonide group (mean dose, 240 microg/d vs 320 microg/d, respectively) and with 77% fewer oral steroid treatment days vs budesonide (114 days vs 498 days, respectively). Both treatments were well tolerated. CONCLUSIONS: Budesonide/formoterol for both maintenance and relief improves asthma control with a lower steroid load compared with a higher dose of budesonide plus terbutaline.     

Age and the Impacts of Triggers in Childhood Asthma

This study examined the relationships among age (2-20 years) and the impacts of 12 common triggers in episodes of childhood asthma. The triggers were: air pollution, allergy problems, cigarette smoke, stress or worry, anger, excitement, laughter, high/low environmental temperature, high humidity, respiratory infection, nighttime hours, and physical activity. Data were analyzed from families with asthmatic children (n = 119) as part of a larger study of biological and psychosocial factors in asthma and other illnesses. Positive correlations were found for age and the trigger impacts of allergy problems (p = 0.025) and physical activity (p = 0.004); negative correlations were found for age and the trigger impacts of nighttime hours (p = 0.002) and respiratory infection (p = 0.002). Age was also negatively correlated with the frequency of recent respiratory infections (p = 0.000) and positively correlated with the intensity of hay fever episodes (p = 0.047). These findings indicate that as children with asthma get older, their asthma episodes are more likely to be influenced by allergy problems and physical activity, and less likely to be associated with nighttime hours and respiratory infections.     

Adrenal function and lipid metabolism in asthmatic children treated with budesonide]

OBJECTIVE: To assess the effect of low doses of inhaled budesonide on the adrenal function and lipid metabolism of asthmatic children. MATERIAL AND METHODS: The study included 10 asthmatic children (mean age, 8.8 years) treated with inhaled budesonide (200-300 micrograms/day) for a period longer than 3 months (group A); 15 asthmatic children (mean age, 7.8 years) without steroid treatment (group B) and 10 non-asthmatic children (group C). Basal cortisol levels, as well as postACTH, adrenal androgens, lipids and urinary cortisol were determined. RESULTS: No significant differences were detected between groups A and B in the studied variables. In asthmatic children, urinary cortisol was significantly higher than in non-asthmatic children. Triglycerides, total cholesterol, low density lipoprotein cholesterol and atherogenic index levels were higher in asthmatic children with and without budesonide treatment, compared with non-asthmatic children. CONCLUSIONS: Treatment of asthmatic children with low doses of inhaled budesonide did not modify the adrenal axis function nor lipid metabolism. Asthmatic patients showed an atherogenic lipid profile which could increase the risk of cardiovascular disease.     

Pharmacokinetic Predisposition to Nicotine from Environmental Tobacco Smoke: A Risk Factor for Pediatric Asthma

During the last decade several studies have shown that children whose parents smoke have higher rates of asthma. Recently, hair concentrations of cotinine have been shown to reflect systemic exposure to this constituent of smoke in both children and adults. At the present time it is not known, however, why some children exposed to passive smoking have asthma while others, similarly exposed, do not. The present study aimed at verifying whether asthmatic children are different from nonasthmatic children exposed to similar degrees of passive smoking in the way their bodies handle nicotine, a constituent of cigarette smoke. Seventy-eight asthmatic children were compared to 86 control children, all attending a consulting pediatric clinic in Toronto. A questionnaire completed by the parents and children detailed the daily number of cigarettes the child was exposed to and the identity of the smokers. Clinical data were extracted from the patients' charts. Urinary (corrected for creatinine) and hair concentrations of cotinine were measured by radioimmunoassays. The asthmatic and control children were of similar age, gender, and ethnic distribution, parental education, and socioeconomic status. Parents of asthmatic children tended to report a lower daily number of cigarettes (7.4 ± 1.3/day vs. 11.2 ± 2.3/day, p = 0.14), and this report agreed with the trend of urinary cotinine (47.1 ± 9.1 ng/mg vs. 62.6 ±11.5 ng/mg, respectively). Conversely, children with asthma had on average twofold higher concentrations of cotinine in their hair (0.696 ± 0.742 ng/mg) than control children (0.386 ± 0.383) (p = 0.0001). In a similar manner, the hair.urine concentration ratio was significantly higher in children with asthma (0.028 ± 0.002) than in their controls (0.18 ± 0.003) (p = 0.0001). These results suggest that under exposure to similar amounts of nicotine, children with asthma have on average twofold higher systemic exposure to this constituent of cigarette smoke. These data suggest that out of all children passively exposed to environmental tobacco smoke, those who exhibit asthma have a higher systemic exposure to nicotine, possibly due to lower clearance rate. This is the first evidence of pharmacokinetic predisposition to environmental tobacco smoke as an etiological factor in pediatric asthma.     

Effect of Intermittent Systemic Corticosteroid on Bone Metabolism in Bronchial Asthma Patients

The purpose of this study was to assess the effect on bone mineral density (BMD) of systemic corticosteroid (SCS) intermittently administered for rescue from asthmatic exacerbation. Through digital image processing and calculation of four other indices, BMD was compared in groups of asthmatic patients receiving inhaled corticosteroid (ICS) alone or ICS plus intermittent SCS. We defined SCS as intermittent administration of the equivalent of 1 mg/day prednisolone in the management of asthma exacerbations during the previous 1 year. Serum NTX, a bone resorption marker, was significantly higher (p = 0.02) in the SCS group than the ICS group. SCS had no effect on BMD, although the frequency of patients at “high-risk” for osteoporosis according to the Female Osteoporosis Self-assessment Tool for Asia (FOSTA) tended to be higher in the SCS group (35%) than in the ICS (28%) or control (10%) group. Because patients in the ICS group already had impaired respiratory function due to repeated asthma exacerbations, it was difficult to determine whether it was asthma itself or SCS that is the risk factor for osteoporosis. In addition, the response of biochemical markers of bone turnover to intermittent SCS remains unclear and likely differs from that elicited by high-dose, short-term, or continuous SCS. That said, relatively low-dose intermittent administration of SCS raised levels of bone resorption markers, which likely reflects altered bone metabolism. Taken together, these findings suggest that, without consideration of its effects on bone, SCS administration should be avoided.     

Comparison of Salmeterol with Beclomethasone in Adult Patients with Mild Persistent Asthma Who Are Already on Low-Dose Inhaled Steroids

Current guidelines on asthma management recommend the early use of inhaled corticosteroids. Recent studies of patients with moderate to severe asthma show that the addition of salmeterol is superior to a further increase of the steroids. In this study with adult, mild persistent asthma patients, we compared the effects of adding salmeterol 50 μg b.i.d. versus beclomethasone dipropionate (BDP) 200 μg b.i.d. (both via Diskhaler dry powder inhaler) to the low-dose inhaled steroids. A double-blind, randomized, parallel-group study was conducted with a run-in period of 2 weeks and a treatment period of 12 weeks. Patients (n = 233) were randomized with a peak expiratory flow (PEF) reversibility of 22 10% (mean ± SD) in the run-in period. The morning PEF was 84 ± 17% predicted and the age was 42 ± 14 years (45% males). The average prestudy inhaled steroid dose was 361 μg daily. Within a week of salmeterol treatment the daily PEF recordings reached maximal levels. At the end of the treatment period the evening PEF remained significantly better in the salmeterol group than in the BDP group (p = 0.036). The PEFs, measured at the general practitioners (GPs) office, were at least 95% of the predicted values and the post-salbutamol values at the end of both treatments. However, the salmeterol group had already obtained this level after 2 weeks and differed significantly from the beclomethasone group (p = 0.003 for percent predicted and p = 0.0007 for post-salbutamol PEF values). The symptom scores and the use of rescue medication showed a similar profile. Quality of life improved with both treatments, but without significant statistical differences between the groups. The frequency of adverse events, typical for beta 2-agonists, was low and showed no differences between the groups. These results showed that the addition of salmeterol is at least as effective as adding beclomethasone in normalizing peak flows and improving asthma control in mild persistent asthma patients. Furthermore, salmeterol has a much faster onset of action.     

Central markers of body fat distribution are important predictors of plasma lipids in elderly men and women

We determined the contribution of body fat distribution, peak VO₂, fat mass, and dietary intake to variation in plasma lipids in elderly individuals. Volunteers were a healthy cohort of older Caucasian women (n = 75, mean age ± SD, 72 ± 5 years) and older men (n = 101, 72 ± 5 years). We determined fat mass from underwater weighing, fat patterning from waist circumference, as well as peripheral and truncal skinfolds, exercise capacity from peak VO₂, and dietary intake from three-day food diaries. Plasma lipid levels were measured in the fasting state and included total cholesterol, high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), and fasting triglycerides. Older women weighed less than older men, but had higher fat mass, truncal, and peripheral skinfolds. Waist circumference and peak VO₂ were lower in older women than older men. Older women had higher total cholesterol (217 ± 31 vs. 197 ± 30; p < 0.01), HDL-C (54 ± 12 vs. 49 ± 14; p < 0.05), and LDL-C (133 ± 26 vs. 121 ± 27; p < 0.01) when compared with older men. No gender differences were noted in fasting triglycerides. Truncal skinfolds were the best predictor of plasma lipids in older men, accounting for between 9% and 30% (r(²) of the variation in plasma lipids. Similarly, in older women, central markers of fatness (i.e., waist circumference and truncal skinfolds) were the best predictors of plasma lipids (r² = 3% to 24%). Total fat mass, peak VO₂ and dietary intake were not independent predictors of plasma lipids in older men and women. Indices of central body fatness, rather than total fat mass, peak VO₂ or dietary intake are stronger predictors of plasma lipids in healthy older men and women.     

Atrial excitability and conduction in patients with interatrial conduction defects

Prolongation of P-wave duration is an accepted indicator of an interatrial conduction disturbance and may predispose patients to atrial arrhythmias. This study was performed to monitor electrophysiologic characteristics of the atria in patients with a prolonged P-wave duration. Atrial excitability and conduction times were compared in 7 patients with a P-wave duration < 115 ms (Group I) and 13 patients with a duration ≥ 115 ms (Group II). In contrast to the Group I patients, most of the 13 patients in Group II had atrial arrhythmias, including sinus nodal dysfunction (3 patients) and a history of atrial fibrillation or ectopic atrial tachycardia (6 patients). Electrophysiologic differences between the 2 groups included a higher late diastolic threshold in Group II (0.8 ± 0.2 mA versus 1.3 ± 0.2 mA; p < 0.005), and a greater increase in intraatrial conduction time (5 ± 10 ms versus 30 ± 20 ms; p < 0.005) and interatrial conduction time (5 ± 15 ms versus 30 ± 15 ms; p < 0.05) of early premature responses. There were no differences between the 2 groups in refractory periods, shape of the strength interval curve, or conduction times of premature responses occurring late in diastole.

These abnormalities in conduction time and excitability found in patients with a prolonged P-wave duration may predispose to the initiation of certain atrial tachyarrhythmias.