Use of inhaled corticosteroids in patients with mild asthma.

A double blind, parallel group study was carried out to investigate the effect of inhaled budesonide in a moderate (200 micrograms) and a low (100 micrograms) twice daily dosage compared with the effect of placebo in 103 adults with mild symptomatic asthma. Subjects recorded peak expiratory flow (PEF), asthma symptoms, and beta 2 agonist consumption at home for a period of seven weeks (a one week run in and six weeks' treatment). Morning baseline PEF (around 80% of predicted normal) increased non-significantly to 88% with 200 micrograms budesonide daily and to 90% (p less than 0.05) with 400 micrograms, compared with 81% with placebo. Evening PEF (around 94% of predicted normal) did not change significantly with active or placebo treatment. By comparison with placebo, there was a significant decrease in nocturnal asthma symptoms and beta 2 agonist consumption. The changes during the day were less pronounced and significant only for 400 micrograms budesonide daily. No significant differences between the two active treatments were detected. It is concluded that low doses of inhaled budesonide are effective in patients with mild symptomatic asthma, particularly for night time symptoms and early morning lung function. The early introduction of inhaled corticosteroids for patients with mild asthma and night time symptoms may improve their quality of life during the night and early morning.     

Long-term effects of inhaled corticosteroids on bone mineral density in older women with asthma or COPD: a registry-based cohort study

Summary

We assessed the association between long-term inhaled corticosteroid (ICS) use and bone mineral density (BMD) in older women with chronic respiratory disease. Women with >?50% adherence to ICS use had very slightly accelerated BMD loss at the total hip compared with those with lower or ICS use.

Introduction

This study evaluated the impact of long-term ICS therapy on bone loss in older women with asthma or chronic obstructive pulmonary disease (COPD).

Methods

We used a population-based bone densitometry registry linked with administrative health data covering the province of Manitoba, Canada (1999–2013), to identify women aged >?40 years who had diagnosed asthma or COPD. ICS exposure was defined as cumulative dispensed days and medication possession ratio (MPR). Associations were examined both cross-sectionally and longitudinally, and results were covariate adjusted.

Results

Among 6561 women with asthma and/or COPD (mean age 65 years [SD?=?11]), compared to no ICS treatment, those in the highest tertile of prior ICS use (≥?720 days) had lower BMD at the femoral neck (??0.09 T-score, 95% CI ??0.16, ??0.02) and total hip (??0.14 T-score, 95% CI ??0.22, ??0.05), but not at the lumbar spine. Over a mean of 5 years of follow-up, the highest tertile of ICS exposure (MPR >?0.5) was associated with a ??0.02 SD/year (95% CI ??0.04, ??0.01) greater decline in total hip BMD relative to non-users, with no significant effect at the femoral neck or lumbar spine. Middle and lower tertiles of ICS use were not associated with baseline or longitudinal change in BMD.

Conclusions

The highest tertile of ICS use was associated with a slightly lower hip BMD at baseline and slightly greater reduction in total hip BMD over time in older women with asthma or COPD. No adverse effects on BMD were seen from low to moderate ICS exposure.

     

First treatment with inhaled corticosteroids and the prevention of admissions to hospital for asthma

BACKGROUND: Early treatment with inhaled corticosteroids appears to improve clinical symptoms in asthma. Whether a first treatment initiated in the year following the recognition of asthma can prevent major outcomes such as admission to hospital has yet to be studied. METHODS: A case-control study nested within a cohort of 13,563 newly treated asthmatic subjects selected from the databases of Saskatchewan Health (1977-1993) was undertaken to investigate the effectiveness of a first treatment with inhaled corticosteroids in preventing admissions to hospital for asthma. Study subjects were aged between five and 44 years at cohort entry. First time users of inhaled corticosteroids were compared with first time users of theophylline for a maximum of 12 months of treatment. The two treatments under study were further classified into initial and subsequent therapy to minimize selection bias and confounding by indication. Odds ratios associated with hospital admissions for asthma were estimated using conditional logistic regression. Markers of asthma severity, as well as age and sex, were considered as potential confounders. RESULTS: Three hundred and three patients admitted to hospital with asthma were identified and 2636 matched controls were selected. subjects initially treated with regular inhaled corticosteroids were 40% less likely to be admitted to hospital for asthma than regular users of theophylline (odds ratio 0.6; 95% CI 0.4 to 1.0). The odds ratio decreased to 0.2 (95% CI 0.1 to 0.5) when inhaled corticosteroids and theophylline were given subsequently. CONCLUSION: The first regular treatment with inhaled corticosteroids initiated in the year following the recognition of asthma can reduce the risk of admission to hospital for asthma by up to 80% compared with regular treatment with theophylline. This is probably due, at least in part, to reducing the likelihood of a worsening in the severity of asthma.     

Effects of inhaled tumour necrosis factor alpha in subjects with mild asthma

BACKGROUND: Inhaled tumour necrosis factor alpha (TNF alpha) has previously been shown to induce airway neutrophilia and increased airway reactivity in normal subjects. It was hypothesised that a similar challenge would increase airway reactivity in those with mild asthma, but that the inflammatory profile may differ. METHODS: Ten mild asthmatic subjects were recruited on the basis of clinical asthma and either a sensitivity to methacholine within the range defined for asthma or a 20% improvement in forced expiratory volume (FEV(1)) after 200 micro g salbutamol. Subjects inhaled either vehicle control or 60 ng recombinant human (rh)TNF alpha and were studied at baseline, 6, 24, and 48 hours later. Variables included spirometric parameters, methacholine provocative concentration causing a 20% fall in FEV(1) (PC(20)), induced sputum differential cell count, relative sputum level of mRNA of interleukins (IL)-4, IL-5, IL-9, IL-14, IL-15 and TNF alpha, and the exhaled gaseous markers of inflammation, nitric oxide and carbon monoxide. RESULTS: PC(20) showed an increase in sensitivity after TNF alpha compared with control (p<0.01). The mean percentage of neutrophils increased at 24-48 hours (24 hour control: 1.1 (95% CI 0.4 to 2.7) v 9.2 (95% CI 3.5 to 14.9), p<0.05), and there was also a rise in eosinophils (p=0.05). Relative levels of sputum mRNA suggested a rise in expression of TNF alpha, IL-14, and IL-15, but no change in IL-4 and IL-5. Spirometric parameters and exhaled gases showed no significant change. CONCLUSION: The increase in airway responsiveness and sputum inflammatory cell influx in response to rhTNF alpha indicates that TNF alpha may contribute to the airway inflammation that characterises asthma.     

Bone mineral density and fractures in older men with chronic obstructive pulmonary disease or asthma

Summary  

In 5,541 community dwelling men, chronic obstructive pulmonary disease, or asthma was associated with lower bone mineral density (BMD) at the spine and total hip and an increased risk of vertebral and nonvertebral fractures independent of age, body mass index, and smoking. Men prescribed with corticosteroids had the lowest BMD.     

吸入糖皮质激素治疗对COPD患者的骨密度及骨折风险的影响

目的观察吸入糖皮质激素治疗对慢性阻塞性肺疾病(chronic obstructive pulmonary diseases,COPD)患者的骨密度及骨折风险的影响。方法 122例COPD患者,70例吸入糖皮质激素的当前使用者和52例从未接受过糖皮质激素治疗的患者,进行了骨密度(bone mineral density,BMD)和身体成分评估,并接受了椎体骨折评估(verterbral fracture assessment,VFA)。考虑用于分析的骨病的风险因素是年龄、性别、吸入糖皮质激素使用、体质量指数(body mass index,BMI)、肌肉质量指数(muscle mass index,MMI)和慢性阻塞性肺病全球倡议(GOLD)类别。同时还使用了针对汉族人群的骨折风险评估工具(FRAX)计算工具。结果这些组间在性别、BMI、MMI、GOLD等级、BMD T评分和Z评分的最低值,骨质疏松症的患病率或年龄的低BMD方面没有差异(P0.05)。在使用吸入糖皮质激素的14例患者中通过VFA鉴定椎骨骨折,并且在没有接受糖皮质激素的患者中通过VFA鉴定椎体骨折(P0.05)。MMI与骨质疏松症之间存在关联的趋势(P0.05),并且根据通过GOLD评分评估的COPD严重性,BMD Z评分逐渐降低。椎体骨折与骨质疏松症(P0.05)或低MMI(P0.05)无关。FRAX没有估计骨折风险。结论吸入糖皮质激素可导致骨密度降低,但是骨折风险未发现增加。     

Bone mineral density in asthmatic women on high-dose inhaled beclomethasone dipropionate

Inhaled corticosteroids are the cornerstone of the modern therapy for asthma. In recent years, inhaled corticosteroids have been used in higher doses than previously. This has caused concern about possible osteoporotic side-effects. We studied bone mineral densities (BMDs) in 19 non-smoking women (mean age 53 years, range 40–63) with newly diagnosed bronchial asthma and 19 voluntary healthy nonsmoking women (mean age 53 years, range 43–67). In both groups, 13 subjects were postmenopausal. Patients started beclomethasone dipropionate from the spacer 500 μg twice daily as the sole corticosteroid therapy. BMDs were measured with dual-energy x-ray absorptiometry (DEXA) at the lumbar spine (L2–4) and at the left proximal femur (the neck, Ward's triangle and the trochanteric region). The measurements were made at baseline and 6 and 12 months thereafter. No significant changes were observed in the measured BMDs in either study group. The results show that inhaled beclomethasone dipropionate therapy 1000 μg/day for one year does not affect BMD. Further studies are needed to assess the effects of inhaled corticosteroid on BMD during a longer treatment period.     

Bone mineral density in post-menopausal female subjects is associated with serum antioxidant carotenoids

Summary High intake of fruit and vegetables may reduce the risk of osteoporosis. Carotenoids exist in abundance in these foods. This study showed the association of bone mineral density with serum carotenoids. The findings suggest that β-cryptoxanthin and β-carotene might provide benefits to bone health in post-menopausal female subjects. Introduction Antioxidant carotenoids are abundant in fruit and vegetables. Recent epidemiological studies show that high intakes of fruit and vegetables may reduce the risk of osteoporosis, but little is known about the association of bone mineral density (BMD) with serum carotenoids. Methods A total of 699 subjects (222 males and 477 females) who had received health examinations in the town of Mikkabi, Shizuoka Prefecture, Japan, participated in the study. Radial BMD was measured using dual-energy X-ray absorptiometry (DXA). The associations of serum carotenoid concentrations with the radial BMD were evaluated cross-sectionally. Results In male and pre-menopausal female subjects, the six serum carotenoids were not associated with the radial BMD. On the other hand, in post-menopausal female subjects, serum β-cryptoxanthin and β-carotene were weakly but positively correlated with the radial BMD. After adjustment for confounders, the odds ratio (OR) for the lowest quartile of BMD in the high groups (Q2–Q4) of serum β-cryptoxanthin against the lowest quartile (Q1) was 0.45 (95% confidence interval: 0.22–0.95) in post-menopausal female subjects. However, this association was not significant after further adjusting for intakes of minerals and vitamins. Conclusions Antioxidant carotenoids, especially β-cryptoxanthin, significantly but partly associate with the radial BMD in post-menopausal female subjects.     

Bone mineral density is not diminished by mild to moderate chronic renal insufficiency

BACKGROUND: Persons with end-stage renal disease are at higher risk for osteopenia and hip fracture relative to the age-matched general population. Persons with mild to moderate chronic renal insufficiency (CRI) may have reduced bone mineral density (BMD) as a result of abnormalities in acid-base and vitamin D-parathyroid hormone homeostasis. METHODS: We analyzed data on 13,848 adults aged 20 and above from the Third National Health and Nutrition Examination Survey (NHANES III; 1988-1994). Regression models were used to determine the relationship between femoral BMD and renal function, the latter assessed using serum creatinine, blood urea nitrogen or Cockcroft-Gault creatinine clearance. To control for confounding, we fit sex-stratified models that adjusted for age, weight, height, race-ethnicity, menopausal status, estrogen use, activity level, family history of osteoporosis, diuretic use, and dietary intake of calcium and alcohol. RESULTS: Although subjects with reduced renal function had significantly lower femoral BMD in unadjusted analysis, the association between CRI and bone mineral density was extinguished after adjustment in the multivariate models. In fact, controlling for only sex, age and weight was sufficient to extinguish any negative association between decreased renal function and decreased bone mineral density. CONCLUSION: Although subjects with worse renal function have significantly lower femoral BMD, this association can be explained by confounding, principally by sex, age and weight. After taking into account the facts that women, older individuals and smaller individuals have less renal function and lower BMD, renal function itself is not independently associated with BMD.     

Influence of cigarette smoking on inhaled corticosteroid treatment in mild asthma

Background: Although inhaled corticosteroids have an established role in the treatment of asthma, studies have tended to concentrate on non-smokers and little is known about the possible effect of cigarette smoking on the efficacy of treatment with inhaled steroids in asthma. A study was undertaken to investigate the effect of active cigarette smoking on responses to treatment with inhaled corticosteroids in patients with mild asthma. Methods: The effect of treatment with inhaled fluticasone propionate (1000 µg daily) or placebo for 3 weeks was studied in a double blind, prospective, randomised, placebo controlled study of 38 steroid naïve adult asthmatic patients (21 non-smokers). Efficacy was assessed using morning and evening peak expiratory flow (PEF) readings, spirometric parameters, bronchial hyperreactivity, and sputum eosinophil counts. Comparison was made between responses to treatment in non-smoking and smoking asthmatic patients. Results: There was a significantly greater increase in mean morning PEF in non-smokers than in smokers following inhaled fluticasone (27 l/min v –5 l/min). Non-smokers had a statistically significant increase in mean morning PEF (27 l/min), mean forced expiratory volume in 1 second (0.17 l), and geometric mean PC₂₀ (2.6 doubling doses), and a significant decrease in the proportion of sputum eosinophils (–1.75%) after fluticasone compared with placebo. No significant changes were observed in the smoking asthmatic patients for any of these parameters. Conclusions: Active cigarette smoking impairs the efficacy of short term inhaled corticosteroid treatment in mild asthma. This finding has important implications for the management of patients with mild asthma who smoke.     

Bone mineral density in patients beginning hemodialysis treatment

BACKGROUND: Our study was designed to determine bone mineral density (BMD) in patients beginning hemodialysis (HD) treatment, a possible correlation with the duration of renal failure prior to treatment, a possible correlation with the basic disease and the association with the concentration of intact parathormone (iPTH). METHODS: Our prospective clinical trial included 50 patients beginning HD treatment. Cortical bone mineral density (BMDc) was measured at the left femoral neck and trabecular bone mineral density (BMDt) in the region of the lumbosacral spine. Bone mineral density (BMD) was measured by quantitative digital radiography using a Hologic 2000 plus device belonging to the third generation of densitometers based on dual-energy X-ray absorptiometry. RESULTS: In patients (PTS) beginning HD, the average BMDc was 82 +/- 15% of BMDc in a healthy population of corresponding age and sex. The average BMDt was 91 +/- 16% of BMDt in a healthy population of corresponding age and sex. The difference was statistically significant (p < 0.05). There is a negative correlation between iPTH and BMDc r = -0.34 (p < 0.02). Patients with chronic glomerulonephritis (GN) had a statistically significantly higher BMDc (g/cm(2)) (p < 0.01) than those with analgetic nephropathy (AN). PTS with AN have lower BMDc (g/cm(2), %) (p < 0.02) and BMDt (p < 0.005) than the rest of the PTS, iPTH in PTS with AN is higher than in the rest of the PTS (p < 0.05). CONCLUSIONS: In PTS at the beginning of HD, BMD is lower than in healthy people of corresponding age and sex. This means that BMD already decreases prior to HD. BMDc was statistically significantly lower than BMDt (p < 0.00005). PTS with AN have lower BMD than those with GN and all remaining PTS. A negative correlation between iPTH and BMDc was found.     

哮喘患者感知控制力对糖皮质激素吸入治疗依从性的影响

目的探讨哮喘患者感知控制力对吸入糖皮质激素治疗依从性的影响,为提高患者糖皮质激素治疗依从性提供参考。方法采用方便抽样方法,选取哮喘患者,采用一般资料问卷、哮喘感知控制力问卷(PCAQ)、支气管哮喘用药依从性量表(MARS-A)进行调查。结果 118例患者的感知控制力总分为33.04±4.57;39.83%的患者吸入糖皮质激素治疗依从性好,60.17%的患者吸入糖皮质激素治疗依从性差;ICS治疗依从性与心理控制源、自我效能感呈正相关(r=0.678、0.653,均P0.01),与习得无助感呈负相关(r=-0.636,P0.01);文化程度、家族史、自我效能感、心理控制源和习得无助感是ICS治疗依从性的影响因素(均P0.01)。结论哮喘患者感知控制力水平低可影响糖皮质激素治疗依从性,提高哮喘患者感知控制力水平,恢复其对生活和疾病的控制,可以更好地提高哮喘患者ICS治疗的依从性。     

Effect of inhaled corticosteroids on bronchial responsiveness in patients with "corticosteroid naive" mild asthma: a meta-analysis

BACKGROUND: Inhaled corticosteroids are the most efficacious anti-inflammatory drugs in asthma. International guidelines also advocate the early introduction of inhaled corticosteroids in corticosteroid naive patients. A study was undertaken to assess the effects of inhaled corticosteroids on bronchial hyperresponsiveness in patients with corticosteroid naive asthma by conventional meta-analysis. METHODS: A Medline search of papers published between January 1966 and June 1998 was performed and 11 papers were selected in which the patients had no history of treatment with inhaled or oral corticosteroids. Bronchial responsiveness to bronchoconstricting agents was considered as the main outcome parameter. Doubling doses (DD) of histamine or methacholine were calculated. RESULTS: The total effect size of inhaled corticosteroids (average daily dose 1000 microg) versus placebo in the 11 studies was +1.16 DD (95% confidence interval (CI) +0.76 to +1.57). When only the eight short term studies (2-8 weeks) were analysed the effect size of the bronchoconstricting agent was +0.91 DD (95% CI +0.65 to +1.16). No relationship was found between the dose of inhaled corticosteroid used and the effect on bronchial responsiveness. CONCLUSION: This meta-analysis in patients with corticosteroid naive asthma indicates that, on average, high doses of inhaled corticosteroids decrease bronchial hyperresponsiveness in 2-8 weeks. It remains unclear whether there is a dose-response relationship between inhaled corticosteroids and effect on bronchial hyperresponsiveness.     

Bone mineral density and urine calcium excretion among subjects with and without nephrolithiasis

BACKGROUND: Bone mineral density (BMD) is reduced among patients with idiopathic hypercalciuria (IH) and nephrolithiasis. To disentangle effects of diet, stone formation, and physiology upon BMD, we studied vertebral and femoral neck BMD among relatives of hypercalciuric stone formers, and contrasted those with to those without stones. METHODS: Among 59 subjects from 11 families, vertebral and femoral neck BMD, diet calcium intake, urine excretions of calcium, sodium, ammonium, titratable acid, sulfate, urea nitrogen, and serum levels of calcitriol and markers of bone turnover were studied. RESULTS: Stone formers (SF) consumed less calcium than non-stone formers (NSF). Spine and femoral neck BMD z-scores varied inversely with urine calcium loss and urine ammonium excretion among SF but not NSF. No correlations of BMD z-score were found for bone markers, calcitriol, or any of the other measurements. CONCLUSION: SF consumed less calcium, presumably to prevent more stones, and displayed a bone mineral responsiveness to calcium loss and ammonium excretion not present among NSF, who ate more calcium. Lowered calcium consumption in IH, perhaps in response to stone formation, alters bone responses in a direction that can predispose to mineral loss and eventual fracture.     

Bone mineral density in women with sarcoidosis

Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Almost any organs of the body, but mostly the lungs, are involved. Bone mineral density (BMD) can be affected directly or indirectly in chronic granulomatous systemic diseases such as sarcoidosis. The aim of our study was to evaluate BMD in premenopausal and postmenopausal sarcoidosis patients with or without prednisone treatment and to compare their BMD values with those of a control group having the same menopausal status. Thirty-five premenopausal women (18 untreated, 8 treated, and 9 controls) and 21 postmenopausal women (5 untreated, 5 treated, and 11 controls) were included in the study. All of the patients had a histologically proven diagnosis and were being followed-up at the Sarcoidosis Outpatient Clinic of our unit. BMD of the lumbar (L) spine and femoral neck was measured by dual-energy absorptiometry (DEXA). The subgroups of premenopausals and postmenopausals were compared separately. Comparison among the groups was performed by using analysis of variance. Age, duration of the disease, and body mass index were comparable in treated, untreated, and control subgroups of the pre- and postmenopausal groups, and the subgroups of postmenopausals had comparable durations since menopause. For premenopausals, BMD values at L1–4 were not significantly different among the subgroups (0.920 ± 0.08g/cm², 0.801 ± 0.09g/cm², and 0.910 ± 0.05g/cm², for untreated, treated, and controls, respectively). However, the BMD value at the femoral neck in treated patients (0.921 ± 0.1g/cm²) was significantly lower than the values in untreated patients (1.080 ± 0.2g/cm²; P 0.01) and in controls (1.028 ± 0.17g/cm²; P 0.05). For postmenopausals, the BMD value at L1–4 in controls (1.019 ± 0.07g/cm²) was significantly higher than the values in untreated patients (0.783 ± 0.01g/cm²) and in treated patients (0.751 ± 0.08g/cm²; P 0.001 for both). The BMD value at the femoral neck in controls (0.890 ± 0.1g/cm²) was higher than the values in untreated patients (0.745 ± 0.08g/cm²) and treated patients (0.747 ± 0.1g/cm²), but the difference was not statistically significant (P = 0.06). We concluded that sarcoidosis patients, especially postmenopausal patients with corticosteroid treatment, may have an increased risk of bone mineral loss. Large-scale studies are warranted in order to delineate the exact roles of the disease itself, menopausal status, and corticosteroid treatment in this bone mineral loss.