慢性阻塞性肺疾病急性加重期患者血清瘦素、甲状腺激素水平与营养状况及肺功能的相关性
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摘要
目的
探讨慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)急性加重期患者血清瘦素、甲状腺激素水平及其相关性,以及与营养状况、肺功能的关系,以进一步探讨COPD并发营养不良的机制及营养不良对COPD患者肺通气功能及免疫防御功能的影响,为临床治疗提供理论依据。方法
1.研究对象
(1)COPD组:选择我院呼吸内科收治的COPD患者45例,其诊断符合2007年中华医学会制定的COPD诊治指南,经肺功能检查证实有不可逆的气道阻塞;患者未接受营养支持治疗,并排除合并有影响代谢和营养状况的其它疾病,如活动性结核、恶性肿瘤、甲状腺功能亢进、糖尿病及肝、肾功能衰竭等;病情严重不能完成肺功能检查者不选入本研究。将符合体重指数(body mass index , BMI)<20 ,且伴理想体重百分比(ideal body weight ,IBW%)<90%;血清白蛋白(albumin,ALB)<35g/L;淋巴细胞计数(total lymphocyte count,TLC)<1.2×109/L中两项者归入COPD营养不良组,其余归入非营养不良组。
(2)健康对照组:20名,经病史、查体及辅助检查,排除心、脑、肺、肾等疾病,近两个月内无全身感染史。
2.营养指标的测定
全体观察对象均测定身高、体重、ALB、TLC,并计算BMI、IBW%,以评价他们的营养状态。
3.血清甲状腺激素、瘦素和的测定
所有研究对象于清晨空腹采取肘静脉血6ml注入到干燥的试管中,4℃静置30min后用台式离心机以3000转/分离心15min,分离得血清,分装,-70℃冻存待用。同批专人采用放射免疫法(radio immunity,RIA)测定血清三碘甲腺原氨酸(triiodothyronine,T3)、甲状腺素(tetraiodothyronine,T4)、促甲状腺激素(thyrotropic-stimulating hormone,TSH)及血清瘦素的浓度。
4.T细胞亚群检测
采集受试者清晨空腹静脉血2ml,离心分离血清, -20℃冷冻待用。采用流式细胞仪检测,严格按试剂盒说明操作。
5.肺通气功能的测定
所有受试者均用肺功能仪进行测定。主要测定指标为最大通气量(maximal ventilatory volume,MVV%)、用力肺活量(forced vital capacity,FVC%)、第一秒用力呼气容积(forced expiratory volume in one second,FEV1%)、第一秒用力呼气容积占用力肺活量的比值(FEV1/FVC)。
结果
一、COPD患者营养状况
与对照组比较,CODP组的年龄和性别构成比比较差异均无统计学意义(P>0.05),但两组营养参数的比较差异有统计学意义(P<0.05)。
二、血清甲状腺素、瘦素水平测定结果
COPD组血清T3、T4低于对照组,其中T3含量显著降低(P<0.01),TSH含量与对照组比较差异无统计学意义(P>0.05);瘦素水平显著低于对照组(P<0.01)。
三、血清T细胞亚群、肺功能指标测定结果
COPD患者与对照组比较CD3、CD4、CD4/CD8降低, CD8升高,差异有显著性(P<0.05)。
四、COPD营养不良组和非营养不良组血清营养参数、免疫状况、肺功能指标、甲状腺素、瘦素水平比较
营养不良组和非营养不良组ALB、TLC、CD3、CD4、CD8、CD4/CD8、瘦素、T3、TSH比较均有统计学意义,其中,营养不良组ALB、TLC、CD3、CD4、CD8、CD4/CD8、瘦素显著低于非营养不良组(P<0.01)。
五、COPD患者血清ILIB、瘦素与营养参数及肺功能指标的关系
直线相关分析表明,CODP患者血清T3与营养参数中的BMI呈高度正相关(r= 0.496,P<0.01),与MVV%、FVC%呈正相关(P<0.05或P<0.001);瘦素BMI、IBW%呈显著正相关(P<0.001),与MVV%呈正相关(r=0.302,P<0.05);血清瘦素和TSH呈正相关(r=0.902,P<0.001))。
结论
1.对COPD患者的营养评价表明:COPD常合并营养不良,临床表现为人体测量、生化及免疫指标异常。
2.血清瘦素、T3浓度与COPD的营养状态密切相关, T3和瘦素有相关性,它们共同参与了营养不良的形成。
3慢性阻塞性肺疾病患者的甲状腺素水平、瘦素水平与免疫功能、肺功能指标有相关性,可以用于指导营养支持等临床治疗以及观察预后的指标。
Objective
To discuss the correlation between Serum Leptin ,Thyroid Hormones and Nutritional State, Pulmonary function test in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease to explore the pathophysiology of nutritional depletion in COPD and its effect on pulmonary function and immune function in order to provide theorial evidence for reasonable nutritional treatment in COPD patients with malnutrition.
Methods
1.object:
(1) COPD group:
45 cases of COPD, diagnosed according as the COPD guide Published in 2007, were enrolled in the study. They did not receive nutritional support and they have no other diseases as can influence organism metabolismand nutritional status.Such as active tuberculosis、malignant tumor、hyperthyroidism、diabetes and Liver function or kidney functional disturbance and other wasting disease.
(2) Control group:
18 healthy people were enrolled in study after the evenlation of history, physical inspection, auxiliary examination and without systemic infection in reneent 2 months.
2. Measurement of the signal of nutrition:
The height, bodyweight, BMI, %IBW, ALB and TLC were measured in all subjects to assess their nutritional status.
3. Measure thyroid hormones and leptin in blood serum:
6 ml vein blood was collected from all subjects in the morning and separated serum through centrifuge 15 minutes with a speed of 3000rm/in,after standing for 30 minutes and put the serum into the icebox below zero 70 degree. we measured the levels of T3,T4,TSH and Leptin in serum by radio immunoassay.
4. Measure T lymphocyte subgroup in blood serum: 6 ml vein blood was collected from all subjects, separated serum and put the serum into the icebox below zero 20 degree we measured the levels of T lymphocyte subgroup by flow cytometry.
5. Pulmonary test:
All the subjects received pulmonary function test,the main indext were as follows: MVV%,FVC%,FEVI% and FEVI/FVC.
Results
1. Nutritional state in COPD group:
Comparing with the control group,there was no significant deviation with age and sex in COPD group(P>0.05). However, there was significant deviation with the state of nutrition between the two groups.
2. Thyroid hormones and leptin in blood serum:
Comparing with the control group, the levels of T3、T4 in blood serum of COPD group is below (P<0.05),and T3 was lower significantly .there was no significant difference with TSH between the two groups. conclusion of leptin in blood serum of COPD group is significantly below to control group. (P<0.01)
3. T lymphocyte subgroup and pulmonary function index in blood serum:
Comparing with the control group, CD3、CD4、CD4/CD8 was lower and CD8 was higher in COPD group,and the difference was statistically significant . (P<0.05)
4. Comparing nutrition parmater、T lymphocyte subgroup、pulmonary function index、thyroid hormones and leptin between malnutrition group and none malnutrition group:
There was statistically significant difference between the malnutrition group and none malnutrition group in ALB、TLC、CD3、CD4、CD8、CD4/CD8、leptin、T3 and TSH. ALB、TLC、CD3、CD4、CD8、CD4/CD8 and leptin were significantly lower in malnutrition group than none malnutrition group. (P<0.01)
5. The levels of thyroid hormones and letin and their relationship to nutritional state,immune function,pulmonary test:
By the analysis of 1inear correlation,T3 was positivly correlated with MVV%、FVC%(P<0.05或P<0.001); and even more with BMI(r= 0.496,P<0.01), the leptin was positivly correlated with MVV%(r=0.302,P<0.05), and even more with MVV%、FVC%(P<0.001); the leptin was positivly correlated with TSH(r=0.902,P<0.001)).
Conclusion
1.The evaluation of the nutritional status of patients with COPD shows that nutritional
depletion is prevalent in COPD patients whose clinical manifestation includes the abnormalities of the althropometric measurement,biochemical andimmuno- logical criterion.
2.There was closely correlation between triiodothyronine,leptin and nutritional status in COPD. Serum triiodothyronine correlates with leptin levels, which contributes to the malnutrition in COPD patients.
3. There was correlation between the levels of thyroid hormones, leptin and immune function,pulmonary function test in the patients of COPD,which could be used a prognostic factor and help the clinical treatment of nutritional support.
探讨慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)急性加重期患者血清瘦素、甲状腺激素水平及其相关性,以及与营养状况、肺功能的关系,以进一步探讨COPD并发营养不良的机制及营养不良对COPD患者肺通气功能及免疫防御功能的影响,为临床治疗提供理论依据。方法
1.研究对象
(1)COPD组:选择我院呼吸内科收治的COPD患者45例,其诊断符合2007年中华医学会制定的COPD诊治指南,经肺功能检查证实有不可逆的气道阻塞;患者未接受营养支持治疗,并排除合并有影响代谢和营养状况的其它疾病,如活动性结核、恶性肿瘤、甲状腺功能亢进、糖尿病及肝、肾功能衰竭等;病情严重不能完成肺功能检查者不选入本研究。将符合体重指数(body mass index , BMI)<20 ,且伴理想体重百分比(ideal body weight ,IBW%)<90%;血清白蛋白(albumin,ALB)<35g/L;淋巴细胞计数(total lymphocyte count,TLC)<1.2×109/L中两项者归入COPD营养不良组,其余归入非营养不良组。
(2)健康对照组:20名,经病史、查体及辅助检查,排除心、脑、肺、肾等疾病,近两个月内无全身感染史。
2.营养指标的测定
全体观察对象均测定身高、体重、ALB、TLC,并计算BMI、IBW%,以评价他们的营养状态。
3.血清甲状腺激素、瘦素和的测定
所有研究对象于清晨空腹采取肘静脉血6ml注入到干燥的试管中,4℃静置30min后用台式离心机以3000转/分离心15min,分离得血清,分装,-70℃冻存待用。同批专人采用放射免疫法(radio immunity,RIA)测定血清三碘甲腺原氨酸(triiodothyronine,T3)、甲状腺素(tetraiodothyronine,T4)、促甲状腺激素(thyrotropic-stimulating hormone,TSH)及血清瘦素的浓度。
4.T细胞亚群检测
采集受试者清晨空腹静脉血2ml,离心分离血清, -20℃冷冻待用。采用流式细胞仪检测,严格按试剂盒说明操作。
5.肺通气功能的测定
所有受试者均用肺功能仪进行测定。主要测定指标为最大通气量(maximal ventilatory volume,MVV%)、用力肺活量(forced vital capacity,FVC%)、第一秒用力呼气容积(forced expiratory volume in one second,FEV1%)、第一秒用力呼气容积占用力肺活量的比值(FEV1/FVC)。
结果
一、COPD患者营养状况
与对照组比较,CODP组的年龄和性别构成比比较差异均无统计学意义(P>0.05),但两组营养参数的比较差异有统计学意义(P<0.05)。
二、血清甲状腺素、瘦素水平测定结果
COPD组血清T3、T4低于对照组,其中T3含量显著降低(P<0.01),TSH含量与对照组比较差异无统计学意义(P>0.05);瘦素水平显著低于对照组(P<0.01)。
三、血清T细胞亚群、肺功能指标测定结果
COPD患者与对照组比较CD3、CD4、CD4/CD8降低, CD8升高,差异有显著性(P<0.05)。
四、COPD营养不良组和非营养不良组血清营养参数、免疫状况、肺功能指标、甲状腺素、瘦素水平比较
营养不良组和非营养不良组ALB、TLC、CD3、CD4、CD8、CD4/CD8、瘦素、T3、TSH比较均有统计学意义,其中,营养不良组ALB、TLC、CD3、CD4、CD8、CD4/CD8、瘦素显著低于非营养不良组(P<0.01)。
五、COPD患者血清ILIB、瘦素与营养参数及肺功能指标的关系
直线相关分析表明,CODP患者血清T3与营养参数中的BMI呈高度正相关(r= 0.496,P<0.01),与MVV%、FVC%呈正相关(P<0.05或P<0.001);瘦素BMI、IBW%呈显著正相关(P<0.001),与MVV%呈正相关(r=0.302,P<0.05);血清瘦素和TSH呈正相关(r=0.902,P<0.001))。
结论
1.对COPD患者的营养评价表明:COPD常合并营养不良,临床表现为人体测量、生化及免疫指标异常。
2.血清瘦素、T3浓度与COPD的营养状态密切相关, T3和瘦素有相关性,它们共同参与了营养不良的形成。
3慢性阻塞性肺疾病患者的甲状腺素水平、瘦素水平与免疫功能、肺功能指标有相关性,可以用于指导营养支持等临床治疗以及观察预后的指标。
Objective
To discuss the correlation between Serum Leptin ,Thyroid Hormones and Nutritional State, Pulmonary function test in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease to explore the pathophysiology of nutritional depletion in COPD and its effect on pulmonary function and immune function in order to provide theorial evidence for reasonable nutritional treatment in COPD patients with malnutrition.
Methods
1.object:
(1) COPD group:
45 cases of COPD, diagnosed according as the COPD guide Published in 2007, were enrolled in the study. They did not receive nutritional support and they have no other diseases as can influence organism metabolismand nutritional status.Such as active tuberculosis、malignant tumor、hyperthyroidism、diabetes and Liver function or kidney functional disturbance and other wasting disease.
(2) Control group:
18 healthy people were enrolled in study after the evenlation of history, physical inspection, auxiliary examination and without systemic infection in reneent 2 months.
2. Measurement of the signal of nutrition:
The height, bodyweight, BMI, %IBW, ALB and TLC were measured in all subjects to assess their nutritional status.
3. Measure thyroid hormones and leptin in blood serum:
6 ml vein blood was collected from all subjects in the morning and separated serum through centrifuge 15 minutes with a speed of 3000rm/in,after standing for 30 minutes and put the serum into the icebox below zero 70 degree. we measured the levels of T3,T4,TSH and Leptin in serum by radio immunoassay.
4. Measure T lymphocyte subgroup in blood serum: 6 ml vein blood was collected from all subjects, separated serum and put the serum into the icebox below zero 20 degree we measured the levels of T lymphocyte subgroup by flow cytometry.
5. Pulmonary test:
All the subjects received pulmonary function test,the main indext were as follows: MVV%,FVC%,FEVI% and FEVI/FVC.
Results
1. Nutritional state in COPD group:
Comparing with the control group,there was no significant deviation with age and sex in COPD group(P>0.05). However, there was significant deviation with the state of nutrition between the two groups.
2. Thyroid hormones and leptin in blood serum:
Comparing with the control group, the levels of T3、T4 in blood serum of COPD group is below (P<0.05),and T3 was lower significantly .there was no significant difference with TSH between the two groups. conclusion of leptin in blood serum of COPD group is significantly below to control group. (P<0.01)
3. T lymphocyte subgroup and pulmonary function index in blood serum:
Comparing with the control group, CD3、CD4、CD4/CD8 was lower and CD8 was higher in COPD group,and the difference was statistically significant . (P<0.05)
4. Comparing nutrition parmater、T lymphocyte subgroup、pulmonary function index、thyroid hormones and leptin between malnutrition group and none malnutrition group:
There was statistically significant difference between the malnutrition group and none malnutrition group in ALB、TLC、CD3、CD4、CD8、CD4/CD8、leptin、T3 and TSH. ALB、TLC、CD3、CD4、CD8、CD4/CD8 and leptin were significantly lower in malnutrition group than none malnutrition group. (P<0.01)
5. The levels of thyroid hormones and letin and their relationship to nutritional state,immune function,pulmonary test:
By the analysis of 1inear correlation,T3 was positivly correlated with MVV%、FVC%(P<0.05或P<0.001); and even more with BMI(r= 0.496,P<0.01), the leptin was positivly correlated with MVV%(r=0.302,P<0.05), and even more with MVV%、FVC%(P<0.001); the leptin was positivly correlated with TSH(r=0.902,P<0.001)).
Conclusion
1.The evaluation of the nutritional status of patients with COPD shows that nutritional
depletion is prevalent in COPD patients whose clinical manifestation includes the abnormalities of the althropometric measurement,biochemical andimmuno- logical criterion.
2.There was closely correlation between triiodothyronine,leptin and nutritional status in COPD. Serum triiodothyronine correlates with leptin levels, which contributes to the malnutrition in COPD patients.
3. There was correlation between the levels of thyroid hormones, leptin and immune function,pulmonary function test in the patients of COPD,which could be used a prognostic factor and help the clinical treatment of nutritional support.
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[34] RosenbaumM, Leibel RL·The role of leptin in human physiology·N Eng J Med, 1999,341:913-914·
[35]高玮,周新.慢性阻塞性肺疾病患者营养状态与血清瘦素可溶性肿瘤坏死因子体的关系,临床荟萃,2006,21:5
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[12] Larsson H, Elmstahl S,Ahren B. Plasma leptin levels cor-relate to islet function independently of body fat in postmenopausalwomen[J].Diabetes, 1996, 45(11): 1580-1584.
[13]罗勇,徐卫国.慢性阻塞性肺疾病与甲状腺激素相关性研究.上海医学,2000,20(5):273-275.
[14]顾宇彤.慢性阻塞性肺病缓解期患者营养状况对呼吸肌力量的影响.中华内科杂志,1998,37(10):682-685.
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[33] Chen Mingdao, Gu Weiqiong, Tang Jinfeng, et al·Serum leptin leve and adiposity in adult Chinese: a preliminary observation·Chin Med J1999, 112: 801-804·
[34] RosenbaumM, Leibel RL·The role of leptin in human physiology·N Eng J Med, 1999,341:913-914·
[35]高玮,周新.慢性阻塞性肺疾病患者营养状态与血清瘦素可溶性肿瘤坏死因子体的关系,临床荟萃,2006,21:5
[36] Lord GM,Matarese G,Howard JK,et al.Leption modulates the T-cell immune re-sponse and reverses starvation-induced im-munosuppression[J]. Nature, 1998, 394(6696):897
[37] Kakucska I et al. Changes in adrenal stat us affect hypotha lamic thyrotrop- in releasing hormone gene expression in parallel with corticotropin releasing hormone[J].Endocrinology,1995,136:2795
[1] EzzellL,JensenGI·Malnutrition in chronic obstructive pul-monary disease·Am J Clin Nutr,2000,72(6): 1415-1416·
[2] Laaban JP·Nutrition and chronic respiratory failure·AnnInternMed, 2000, 151(7): 542-548·
[3] SevenoaksMJ, StockleyRA·ChronicObstructive PulmonaryDisease, inflame- mation and co-morbidity-a common inflam-matory phenotype? RespirRes, 2006, 7(1): 70·
[4] Pitsiou G, Kyriazis G, Hatzizisi O, et al·Tumor necrosisfactor-alpha serum leve,l weight loss and tissue oxygenationin chronic obstructiv pulmonary disease·RespirMed,2002,96(8): 594-598·
[5] Sridhar. Why do patients with emphysema lose weight J.The Lancet,1995, 345:1190-1191.
[6] Baarends EM, ScholsAM, PannemansDL, etal·Total freeliving energy expenditure in patientswith severe chronicob-structive pulmonary disease·Am J Respir Crit Care Med,1997, 155(2): 549-554·
[7] Schols AM·Pulmonary cachexia·Int J Cardio,l 2002, 85(1): 101-110·
[8] Dore MF,et al.Am J Respir Crit Care Med,1997;155;1535-1540.
[9] Schols AM.TNF-alpha and hypermetabolism in chronicobstructive pulmonary disease.Clin Nutr,1999,18(5):255-257
[10] Rosen baum M, Leibel RL.The role of leptin in human physi-ology[J]. N Eng JMed,1999,341(12): 913-915.
[11] Takabatake N, Nakamura H, Minamihaba O,et a.l Anovelpathophysiologic phenomenon in cachexic patientswith chron-ic obstructive pulmonary disease[ J]. Am J Respir CritCareMed,2001, 163(6): 1314-1319.
[12] Larsson H, Elmstahl S,Ahren B. Plasma leptin levels cor-relate to islet function independently of body fat in postmenopausalwomen[J].Diabetes, 1996, 45(11): 1580-1584.
[13]罗勇,徐卫国.慢性阻塞性肺疾病与甲状腺激素相关性研究.上海医学,2000,20(5):273-275.
[14]顾宇彤.慢性阻塞性肺病缓解期患者营养状况对呼吸肌力量的影响.中华内科杂志,1998,37(10):682-685.
[15]刘建明.慢性阻塞性肺病患者与肺通气功能关系的研究.实用预防医学,2005,12(4):837-838.