Lung function decline in asthma: association with inhaled corticosteroids, smoking and sex

BACKGROUND: Inhaled corticosteroids (ICS) provide short term benefits in asthma but the long term effects are still unknown. METHODS: 281 patients diagnosed with moderate to severe asthma in 1963-75 were re-examined in 1991-9. Information was collected on forced expiratory volume in 1 second (FEV(1)), bronchial hyperresponsiveness, atopy, smoking, use and dosage of oral and ICS. Patients were included in the analyses if they had at least three FEV(1) measurements during two consecutive years after the age of 30 and used ICS during follow up. RESULTS: Analyses were performed on 122 patients. During a median follow up period of 23 years, 71 men and 51 women had on average 37 and 40 individual FEV(1) measurements, respectively. Linear mixed effect models showed that men had a mean annual decline in FEV(1) of 20.6 ml/year less after ICS initiation than before (p = 0.011), and in women the decline in FEV(1) was 3.2 ml/year less (p = 0.73). In individuals with <5 pack years of smoking the decline in FEV(1) was 36.8 ml/year less after ICS institution in men (p = 0.0097) and 0.8 ml/year less in women (p = 0.94), the difference between the sexes being significant (p = 0.045). These effects were not observed in those with > or =5 pack years smoking. A higher daily dose of ICS was associated with a smaller decline in FEV(1) in men (p = 0.006), an effect not observed in women. CONCLUSION: Treatment with ICS in adult patients with moderate to severe asthma was associated with a reduction in the decline in FEV(1) over a 23 year follow up period in men who had smoked <5 pack years. This effect was dose dependent and was not present in women or in men with > or =5 pack years of smoking at follow up. The lack of effect of ICS on the decline in FEV(1) in women needs further study.     

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。     

Inhaled corticosteroids and decline of lung function in community residents with asthma

BACKGROUND: Inhaled corticosteroids (ICS) constitute the cornerstone of treatment for asthma. Many studies have reported beneficial short term effects of these drugs, but there are few data on the long term effects of ICS on the decline in forced expiratory volume in 1 second (FEV(1)). This study was undertaken to determine whether adults with asthma treated with ICS have a less pronounced decline in FEV(1) than those not treated with ICS. METHODS: Two hundred and thirty four asthmatic individuals from a longitudinal epidemiological study of the general population of Copenhagen, Denmark were divided into two groups; 44 were treated with ICS and 190 were not treated with ICS. The annual decline in FEV(1) was measured over a 10 year follow up period. RESULTS: The decline in FEV(1) in the 44 patients receiving ICS was 25 ml/year compared with 51 ml/year in the 190 patients not receiving this treatment (p<0.001). The linear regression model with ICS as the variable of interest and sex, smoking, and wheezing as covariates showed that treatment with ICS was associated with a less steep decline in FEV(1) of 18 ml/year (p = 0.01). Adjustment for additional variables including age, socioeconomic status, body mass index, mucus hypersecretion, and use of other asthma medications did not change these results. CONCLUSIONS: Treatment with ICS is associated with a significantly reduced decline in ventilatory function.     

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。     

绝经后妇女的生殖特征和骨密度相关性研究

目的探讨绝经后妇女生殖特征与骨密度之间的关系。方法 2014年3月至2016年7月入住本院收治的200例绝经后骨质疏松症女性被选为候选人。记录了一些社会人口、生活方式和生殖因素。使用双能X射线吸收测量法测量腰椎1-4(L_(1-4))的BMD。Pearson相关检验和多元回归分析评估生殖因素与骨密度的相关性。结果绝经年龄与骨密度无显著相关性,绝经年数、月经初潮年龄、妊娠次数和总泌乳期与其成负相关。在生殖因素中,调整年龄、体质指数、活动和钙摄入量后,泌乳持续时间和骨密度之间的呈现显著负相关性。结论除延长泌乳总时间外,其他生殖因素与绝经后妇女骨密度无显著相关性。     

Relation of serum serotonin levels to bone density and structural parameters in women

Recent studies have demonstrated an important role for circulating serotonin in regulating bone mass in rodents. In addition, patients treated with selective serotonin reuptake inhibitors (SSRIs) have reduced areal bone mineral density (aBMD). However, the potential physiologic role of serotonin in regulating bone mass in humans remains unclear. Thus we measured serum serotonin levels in a population‐based sample of 275 women and related these to total‐body and spine aBMD assessed by dual‐energy X‐ray absorptiometry, femur neck total and trabecular volumetric BMD (vBMD) and vertebral trabecular vBMD assessed by quantitative computed tomography (QCT), and bone microstructural parameters at the distal radius assessed by high‐resolution peripheral QCT (HRpQCT). Serotonin levels were inversely associated with body and spine aBMD (age‐adjusted R = ?0.17 and ?0.16, P < .01, respectively) and with femur neck total and trabecular vBMD (age‐adjusted R = ?0.17 and ?0.25, P < .01 and < .001, respectively) but not lumbar spine vBMD. Bone volume/tissue volume, trabecular number, and trabecular thickness at the radius were inversely associated with serotonin levels (age‐adjusted R = ?0.16, ?0.16, and ?0.14, P < .05, respectively). Serotonin levels also were inversely associated with body mass index (BMI; age‐adjusted R = ?0.23, P < .001). Multivariable models showed that serotonin levels remained significant negative predictors of femur neck total and trabecular vBMD, as well as trabecular thickness at the radius, after adjusting for age and BMI. Collectively, our data provide support for a physiologic role for circulating serotonin in regulating bone mass in humans. © 2010 American Society for Bone and Mineral Research     

绝经后女性血常规指标与骨髓脂肪含量、骨密度相关性研究

目的 探讨绝经后女性血常规指标与骨髓脂肪含量、骨密度相关性。方法 选取72名绝经后女性(年龄55～79岁),测量受试者身高、体重、红细胞计数、白细胞计数、血小板计数,计算体质量指数（body mass index,BMI）,运用磁共振波谱成像(magnetic resonance spectroscopy,MRS)扫描L3椎体骨髓脂肪含量(fat fraction,FF),通过双能X线吸收检测(dual-energy X-ray absorptiometry,DXA)扫描获取受试者腰椎(L1~4)、左股骨颈及全身骨密度(bone mineral density,BMD)值。评价MRS扫描可重复性,分析红细胞计数、白细胞计数、血小板计数与FF值及BMD值相关性,运用多元逐步回归分析FF值的独立相关因素。结果 L3椎体FF值测量可重复性变异系数(CV)为2.86 %。红细胞计数、白细胞计数、血小板计数与FF呈负相关（P<0.01）;红细胞计数、白细胞计数、血小板计数与腰椎（L1~4）骨密度、左股骨颈骨密度无相关性,与全身骨密度呈负相关（P<0.05）。进一步多元逐步回归分析结果表明：校正了年龄、身高、体重、BMI后,红细胞计数、白细胞计数、血小板计数是影响FF的独立负性相关因素（P<0.05,R2=0.518）。结论 血常规指标（红细胞计数、白细胞计数、血小板计数）与FF及绝经后女性骨密度有一定的相关性,对绝经后女性骨质疏松症的早期诊断与防治有一定指导作用。     

他汀类药物治疗对骨代谢的影响：一项Meta分析

目的旨在从已报道的24项临床随机对照试验(RCTs)来评价他汀类药物对骨形成标志物及骨密度的影响。方法检索PubMed、Web of Science、中国知网(CNKI)、万方数据库、中国循证医学数据库、中国生物医学文献数据库等自建库至2019年11月的他汀类药物治疗骨质疏松的相关RCTs。应用Rev Man5.3和Stata15.1对收集的数据进行Meta分析。结果本研究纳入RCTs文献共24篇,纳入病例治疗组852例,对照组798例。结果表明他汀类药物可显著改善血清骨钙素(OC)水平(SMD=0.22,95%CI:0.06～0.37,I2=0%,P=0.006)、血清骨特异性碱性磷酸酶(BALP)水平(SMD=0.32,95%CI:0.15～0.49,I2=35%,P=0.0002)、血清骨保护素水平(SMD=0.80,95%CI:0.14～1.45,I2=62%,P=0.02)。可明显增加腰椎骨密度(SMD=0.35,95%CI:0.14～0.56,I2=59%,P=0.001)、股骨颈骨密度(SMD=0.32,95%CI:0.03～0.61,I2=75%,P=0.03)、股骨粗隆骨密度(SMD=0.46,95%CI:0.13～0.78,I2=59%,P=0.006)、股骨Ward’s三角区骨密度(SMD=0.36,95%CI:0.01～0.71,I2=77%,P=0.04),而对血清I型原胶原N-端前肽(PINP)水平及全髋骨密度无明显影响。结论研究表明他汀类药物可改善血清骨钙素及骨特异性碱性磷酸酶水平及增加腰椎和股骨的骨密度。他汀类药物用于治疗骨质疏松具有巨大的潜力。由于纳入研究的文献数量少、样本量小,仍需更多大样本量、高质量的随机对照试验为该结论提供依据。     

血清H2S水平与骨密度的相关性初步研究

目的血清H_2S水平与骨质疏松的相关性。方法收集2015年10月至2017年10月112例在江苏昆山地区体检和门诊就诊人员的资料,其中男82例,女30例,年龄25～86岁,平均(51.40±10.60)岁;采用DEXA骨密度仪检测该人群的骨密度,以及采用亚甲基蓝法测定血清H_2S水平。结果体内血清H_2S水平与髋部骨密度呈正相关,与腰椎骨密度无明显相关性。结论血清H_2S水平与髋部骨密度存在相关,可能是髋部骨密度下降的独立危险因素,H_2S可能是骨密度的保护因素。     

体检人群血脂水平及血脂异常分型与骨密度的相关性研究

目的探讨基于体检人群血脂各项指标及不同血脂异常分型与骨密度的关系。方法收集2018年1月至2019年6月在四川省人民医院健康管理中心进行健康体检,骨密度和血脂相关指标完整且年龄18周岁的体检者28 174例,收集体检者的基本信息、各项血脂指标及平均骨密度与T值等资料,按照血脂异常分型进一步将患者分为高胆固醇血症组、高三酰甘油血症组、混合型高脂血症组和血脂正常组,比较各组间骨密度的差异,采用多元线性回归模型分析各血脂指标对骨密度的影响。结果 28 174例体检者中,高胆固醇血症914例(3.2%)、高三酰甘油血症2 266例(8.0%)、混合型高脂血症819例(2.9%)、血脂正常24 175例(85.8%);骨密度正常16 594例(58.9%)、骨量减少或骨质流失8 511例(30.2%)、骨质疏松3 069例(10.9%)。不同血脂异常分型体检者的性别构成、平均年龄、BMI水平、TC、TG、LDL-C、HDL-C水平之间存在差异(P均0.05)。不同血脂异常分型体检者的骨量异常者构成、骨密度和T值的平均水平之间存在差异(P均0.05),高胆固醇血症组和混合型高脂血症组的骨密度水平明显低于对照组及高三酰甘油血症组(P均0.05),而骨量异常者的占比为高胆固醇血症组和混合型高脂血症组的构成比高于对照组及高三酰甘油血症组(P均0.05)。结论加强体检人群高胆固醇血症和混合型高脂血症的骨密度筛查,骨量异常患者应重视血脂水平的监测。     

绝经后女性铁蓄积与骨代谢及机体炎症反应的相关性研究

目的研究绝经后女性铁蓄积与骨代谢及机体炎症反应的相关性。方法将117名绝经后女性体检者按照骨密度(bone mineral density,BMD)值分成3组:骨量正常组(T≥-1)、骨量减少组(-2.5T-1)和骨质疏松组(T≤-2.5)。所有体检者均测定:血清生化指标[钙、磷、25(OH)D、血红蛋白、CRP、白细胞、肌酐、尿酸、丙氨酸氨基转移酶、谷草转氨酶、空腹血糖]、铁代谢指标[血清铁蛋白(Fer)、转铁蛋白(TRF)]、骨代谢指标[Ⅰ型胶原代谢产物(β-CTX、PINP)]。结果绝经后女性随着年龄增大,体内血清铁蛋白升高,铁蓄积增加,患骨质疏松症的风险增加,同时伴随β-CTX、PINP、CRP升高。其中血清铁蛋白与骨密度呈负相关,与β-CTX、PINP、CRP呈正相关。结论绝经后女性体内存在铁蓄积,同时伴有慢性炎症反应,铁蓄积可促进I型胶原蛋白降解,加速骨质疏松的进程。     

坤泰胶囊辅助治疗对绝经后骨质疏松症妇女骨密度、骨代谢和激素水平的影响

目的探讨坤泰胶囊辅助治疗对绝经后骨质疏松症患者骨密度、激素水平和骨代谢的影响。方法 150例绝经后骨质疏松症患者被随机分为治疗组、联合治疗组和对照组,每组50例。治疗组给予雷洛昔芬,联合治疗组给予雷洛昔芬加坤泰胶囊治疗,治疗12个月。检测治疗后两组患者髋部及腰椎的骨密度(bone mineral density,BMD)改变,同时测定血清雌二醇(estradiol,E2)、黄体生成素(luteinizing hormone,LH)、促卵泡剌激素(follicle stimulating hormone,FSH)、骨钙素(OC)和I型胶原交联C-末端肽(CTX-1)的水平,并记录治疗期间出现的药物不良反应。结果对照组的腰椎和髋部BMD在1年后较基线时有不同程度降低,比较差异有统计学意义(P0. 05);治疗1年后,治疗组和联合治疗组髋部及腰椎BMD都有不同程度的升高,且组间比较差异有明显的统计学意义(P0. 05);同时治疗组和联合治疗组血清CTX-1水平均降低,OC水平均升高,两组比较有明显的统计学意义(P0. 05);各组血清FSH和LH水平均降低,E2水平升高,两组比较有明显的统计学意义(P0. 05)。两组患者治疗时均未发现明显药物不良反应。结论坤泰胶囊辅助治疗有助于降低骨转换率,改善性激素水平,改善绝经后女性骨质疏松患者髋部及腰部的骨密度。     

女性正常范围促甲状腺激素水平与骨代谢的相关性研究

目的探讨正常范围内促甲状腺激素(Thyroid Stimulating Hormone,TSH)水平对女性骨代谢指标的影响。方法选取896名甲状腺功能正常的女性,根据TSH水平进行三分位数法分组,未绝经组:T1组(0.27-2.00 mIU/L)、T2组(2.01-2.8mIU/L)及T3组(2.81-4.2 mIU/L);绝经组:T1组(0.27-2.01 mIU/L)、T2组(2.02-3.23 mIU/L)及T3组(3.24-4.2mIU/L)。比较各组间血钙、血磷、25(OH)vitD、腰围、BMI、BMD水平之间差异。spearman相关性分析TSH水平与骨量等级之间的相关性。以BMD作为因变量,对其分层后进行二元Logistic回归分析不同TSH水平对女性骨质疏松发生的影响。结果 (1)绝经期组T1组和T2组的左前臂BMD均明显低于T3组(P0.05),T1组和T2组右跟骨BMD均明显低于T3组(均P0.05);未绝经组3组间各指标无明显差异。(2)绝经组分层后的TSH水平与右跟骨、左前臂骨量等级呈负相关(r=-0.228,P0.05;r=-0.145,P0.05)。未绝经组分层后的TSH水平与右跟骨、左前臂骨量等级无相关性。(3)二元Logistic回归分析:以分组后的右跟骨BMD作为因变量,校正性别、年龄、BMI、腰围、血钙、血磷、25(OH)vitD后,绝经后女性T1组能够增加骨质疏松的风险(OR=2.278,95%CI 1.011～5.132,P0.05)。结论绝经后女性正常范围低水平TSH的骨密度更低,患骨质疏松的风险增高。     

非酒精性脂肪肝与骨密度关联研究的相关进展

非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)是非常常见的与代谢综合征的临床特征密切相关的病理状态,其特点在于肝内三酰甘油的堆积及肝脏病变持续进展。在全球,非酒精性脂肪肝的患病率越来越高,特别是在发展中国家,日渐成为危害公众健康的问题。过去认为胰岛素抵抗和肥胖是非酒精性脂肪肝的主要危险因素,与肥胖有着平行关系,近期倾向于肝脏是涉及多器官及系统的复杂作用的中心,包括骨骼及骨骼肌系统。多个横断面研究也发现,胰岛素抵抗、肥胖除了与NAFLD密切相关外,同时也与骨密度间存在着关联,并且不少研究发现NAFLD患者骨密度及骨量较正常同龄人减少,但具体机制仍未清楚。目前认为导致骨质疏松症骨密度的恶化是与年龄相关的过程,另外,NAFLD的患病率也随着年龄增长而增加,两者均有年龄相关性。但NAFLD与骨密度间是否存在关联,目前尚存在争议,笔者就NAFLD对骨密度的影响及相互关系结合国内外的研究进展进行综述。     

骨质疏松症患者血清骨代谢标志物分析与相关性研究

目的对西安地区部分骨质疏松症患者血清骨代谢标志物进行统计及相关性分析。方法纳入2018年4月至2019年3月经西安市红会医院诊治的原发性骨质疏松症患者295例,检测受试者血清钙(Ca)、磷(P)、碱性磷酸酶(ALP)、维生素D(vitamin D,维生素D)、甲状旁腺素(PTH)、I型前胶原N端肽(P1NP)、β-胶原特殊序列(β-Cross)的水平,运用R统计语言进行统计学处理及Pearson相关性分析。结果在大多数骨质疏松症患者中血清Ca、P是正常的;有20%~30%患者ALP升高;绝大多数患者维生素D缺乏或不足;PTH异常者以升高为主,少数女性患者PTH降低;大多数绝经前女性P1NP、β-Cross正常,在少数绝经前女性及1/3男性中出现升高,小部分绝经后女性出现下降,在小部分绝经后女性中升高。女性骨质疏松症患者中,血清ALP与P1NP、ALP与PTH、维生素D与β-Cross呈正相关(P<0.05),血清Ca与β-Cross、P与ALP、P与β-Cross、P与PTH、ALP与维生素D、ALP与β-Cross、维生素D与P1NP、维生素D与PTH、P1NP与β-Cross呈负相关(P<0.05)。男性骨质疏松症患者中,血清维生素D与β-Cross呈正相关(P<0.05),血清Ca与PTH、ALP与维生素D、维生素D与P1NP、维生素D与PTH、P1NP与β-Cross呈负相关(P<0.05)。结论骨质疏松症患者维生素D缺乏或不足情况严重,了解骨代谢标志物间的相关性有助于更好地理解骨质疏松症骨代谢异常机制。     

Effect of teriparatide on bone mineral density and biochemical markers in Japanese women with postmenopausal osteoporosis: a 6-month dose-response study

The dose-response efficacy and safety with three doses of teriparatide and placebo was assessed, using oncedaily subcutaneous injections for 24 weeks, in Japanese postmenopausal women with osteoporosis at high risk of fracture for reasons of preexisting fracture(s), advanced age, and/or low bone mineral density (BMD). In this multicenter, randomized, placebo-controlled study, 159 subjects were randomized and 154 subjects were included for analysis. Teriparatide (10-μg, 20-μg, and 40-μg doses) showed a statistically significant increase with increasing treatment dose as assessed by the percent change of lumbar spine BMD from baseline to endpoint using Williams’ test when compared with placebo (P < 0.001). The mean (±SD) percent change in lumbar spine, femoral neck, and total hip BMD with the 20-μg dose from baseline to endpoint was 6.40% ± 4.76%, 1.83% ± 7.13%, and 1.91% ± 3.60%, respectively. Rapid and sustained increases in bone formation markers [type I procollagen N-terminal propeptide (PINP), type I procollagen C-terminal propeptide (PICP), and bone-specific alkaline phosphatase (BAP)], followed by late increases in a bone resorption marker [type I collagen cross-linked C-telopeptide (CTX)], were observed for the teriparatide treatment groups (20-μg, 40-μg), suggesting a persistent, positive, balanced anabolic effect of teriparatide. Optimal adherence was achieved by this daily self-injection treatment. Regarding safety, most of the adverse events were mild to moderate in severity. No study drug-or study procedure-related serious adverse events were reported during the treatment period. These results observed in Japanese patients may support the observation that teriparatide stimulates bone formation in patients with osteoporosis at a high risk of fracture.     

固本增骨方治疗老年原发性骨质疏松的随机对照临床试验研究

目的观察固本增骨方治疗老年原发性骨质疏松的临床疗效。方法将确诊为老年原发性骨质疏松症的106例患者随机分为固本增骨方组(53例)和骨健康补充剂组(53例),骨健康补充剂组给予碳酸钙D3咀嚼片1片/次,1次/d;骨化三醇胶丸1粒/次,1次/d,1个月为1疗程,共治疗6个疗程,固本增骨方组在骨健康补充剂组治疗基础上,给予固本增骨方,每日1剂,水煎服,早晚各1次分服,1个月为1疗程,观察6个疗程后判定疗效,采用VAS评分、中医症候评分以及检测骨密度值进行疗效评价,并观察不良反应发生情况。结果治疗后固本增骨方组有效率为94.34%,明显高于阳性药物对照组的84.90%(P<0.05);治疗后,两组患者的VAS评分均较治疗前降低(P<0.05),固本增骨方组明显低于骨健康补充剂组(P<0.05);固本增骨方组和骨健康补充剂组治疗后骨密度值均较治疗前升高(P<0.05),治疗组高于骨健康补充剂组(P<0.05);治疗后两组患者的主要症状评分均较治疗前下降(P<0.05),固本增骨方组低于骨健康补充剂组(P<0.05);治疗后,固本增骨方组1例患者出现胃烧灼感;骨健康补充剂组出现2例恶心、纳差,1例患者出现皮肤过敏,停药后不良反应均自行消失,两组患者不良反应的差别无统计学意义(P>0.05)。结论固本增骨方治疗骨质疏松症患者安全有效,能够增加骨密度、缓解疼痛症状以及主要症状,是一种安全、有效、经济的治疗方法。