Nghiên cứu nồng độ vitamin d huyết thanh ở bệnh nhân bệnh phổi tắc nghẽn mạn tính

B GIO DC V O TO B Y T TRNG I HC Y H NI TRN ANH SNG NGHIÊN CứU NồNG Độ VITAMIN D HUYếT THANH BệNH NHÂN BệNH PHổI TắC NGHẽN MạN TíNH LUN VN THC S Y HC H NI 2016 B GIO DC V O TO B Y T TRNG I HC Y H NI TRN ANH SNG NGHIÊN CứU NồNG Độ VITAMIN D HUYếT THANH BệNH NHÂN BệNH PHổI TắC NGHẽN MạN TíNH Chuyờn ngnh: Ni khoa Mó s: 60720140 LUN VN THC S Y HC Ngi hng dn khoa hc: PGS.TS ng Hng Hoa H NI 2016 LI CM N Trong quỏ trỡnh hc v hon thnh khúa lun tt nghip, tụi ó nhn c s ch bo tn tỡnh ca cỏc Thy, cỏc Cụ, s giỳp ca ngi thõn, bn bố v ng nghip.Vi lũng kớnh trng v bit n sõu sc, tụi xin gi li cm n ti: - Ban giỏm hiu Trng i hc Y H Ni, phũng o to sau i hc Trng i hc Y H Ni ó to iu kin tt nht cho tụi nhng nm thỏng hc ti trng - Cỏn b, nhõn viờn khoa c xng khp- Bnh vin Bch Mai ó giỳp tụi thi gian hc tp, nghiờn cu - Ban giỏm c, th khoa c xng khp, th khoa hụ hp bnh vin E ó giỳp tụi sut quỏ trỡnh hc v lm nghiờn cu ti bnh vin E - PGS.TS ng Hng Hoa Trng khoa c xng khp bnh vin E, ngi ó tn tỡnh hng dn tụi bc u nghiờn cu khoa hc v luụn ng hnh cựng tụi sut quỏ trỡnh hon thnh khúa lun Tụi cng xin chõn thnh cm n cỏc Thy, Cụ hi ng chm lun ó cho tụi nhng ý kin quý bỏu lun ca tụi hon thin hn Tụi xin gi li cm n ti tt c bn bố, ng nghip ó luụn ng viờn, giỳp v ng h tụi quỏ trỡnh hc v hon thnh khúa lun Vi tỡnh cm c bit nht ca mỡnh, tụi xin dnh tng ti ton th ngi thõn gia ỡnh nhng ngi ó luụn sỏt cỏnh bờn tụi cuc sng cng nh hc H Ni, ngy 25 thỏng 11 nm 2016 Trn Anh Sỏng LI CAM OAN Tụi l Trn Anh Sỏng, Cao hc Ni khúa 23, Trng i hc Y H Ni, chuyờn ngnh: Ni khoa, xin cam oan õy l Lun bn thõn tụi trc tip thc hin di s hng dn ca PGS.TS ng Hng Hoa Cụng trỡnh ny khụng trựng lp vi bt k nghiờn cu no khỏc ó c cụng b ti Vit Nam Cỏc s liu v thụng tin nghiờn cu l hon ton chớnh xỏc, trung thc v khỏch quan, ó c xỏc nhn v chp nhn ca c s ni nghiờn cu Tụi xin hon ton chu trỏch nhim trc phỏp lut v nhng cam kt ny H Ni, ngy 25 thỏng 11 nm 2016 Ngi vit cam oan Trn Anh Sỏng DANH MC VIT TT 1,25(OH)2vitamin D: 25(OH)vitamin D: BMI: CAT: MRC: CNHH: COPD: Cs: DBP: TNC: FEV1/FVC: FEV1: FVC: GOLD: 1, 25 dihydroxyvitamin D 25- hydroxyvitamin D Body Mass Index (Ch s c th) COPD Assessment Test Medical Research Council Chc nng hụ hp Chronic Obstructive Pulmonary Disease ( Bnh phi tc nghn mn tớnh) Cng s Vitamin D Binding Protein i tng nghiờn cu Ch s Gaensler Forced Expiratory Volume in one second Forced Vital Capacity Global Initiative for Chronic Obstructive Lung Disease (Chng trỡnh ton cu v qun lý, iu NHLBI: VC: WHO: tr bnh phi tc nghn mn tớnh) National Heart, Lung, And Blood Institute (Vin Huyt hc Tim mch Hụ hp Hoa K) Vital capacity World Health Organisation MC LC T VN CHNG TNG QUAN TI LIU 1.1 Bnh phi tc nghn tớnh 1.1.1 nh ngha bnh phi tc nghn mn tớnh .3 1.1.2 Dch t hc 1.1.3 Yu t nguy c COPD 1.1.4 C ch bnh sinh ca COPD [1], [7], [22] 1.1.5 Gii phu bnh [1], [22] 1.1.6 Chn oỏn v phõn loi bnh phi tc nghn mn tớnh 1.1.7 iu tr COPD .12 1.2 Vitamin D 16 1.2.1 Nguc gc vitamin D 16 1.2.2 Cỏc hp cht vitamin D .17 1.2.3 Chuyn húa vitamin D [28] 17 1.2.4 Chn oỏn thiu vitamin D 21 1.2.5 Chn oỏn nguyờn nhõn thiu vitamin D 22 1.2.6 Nguyờn nhõn gõy thiu vitamin D bnh nhõn COPD 23 1.2.7 Cỏc yu t nh hng n nng vitamin D huyt 23 1.2.8 Vai trũ ca vitamin D c th 24 1.2.9 Cỏc phng phỏp nh lng vitamin D [46] .28 1.2.10 Tỡnh hỡnh cỏc nghiờn cu v thiu vitamin D 29 CHNG 32 I TNG V PHNG PHP NGHIấN CU .32 2.1 a im v thi gian nghiờn cu 32 2.2 i tng nghiờn cu (TNC) 33 2.2.1 Tiờu chun la chn i tng nghiờn cu nhúm bnh 33 2.2.2 Tiờu chun la chn i tng nghiờn cu nhúm chng 34 2.2.3 Tiờu chun loi tr bnh nhõn nghiờn cu 34 2.3 Phng phỏp nghiờn cu 35 2.3.1 Thit k nghiờn cu .35 2.3.2 C mu 35 2.3.3 Bin s v ch s nghiờn cu .35 2.4 X lý s liu .40 2.5 o c nghiờn cu 40 2.6 S nghiờn cu 40 CHNG 41 KT QU NGHIấN CU 41 3.1 c im ca i tng nghiờn cu 41 3.1.1 c im chung ca TNC 41 3.1.2 Mt s c im lõm sng ca nhúm COPD 43 3.2 Mi liờn quan gia nng 25(OH)vitamin D huyt vi mt vi c im lõm sng v cn lõm sng 48 3.2.1 Liờn quan gia nng 25(OH)vitamin D huyt vi tui .48 3.2.2 Liờn quan gia nng 25(OH) vitamin D huyt vi ch s c th (BMI) 49 3.2.3 Liờn quan gia nng 25(OH) vitamin D huyt vi thi gian mc bnh (TGMB) 49 3.2.4 Liờn quan gia nng 25(OH)vitamin D huyt vi tin s hỳt thuc 50 3.2.5 Liờn quan gia nng 25(OH)vitamin D huyt vi s bao nm 51 3.2.6 Liờn quan gia nng 25(OH)vitamin D huyt vi thi gian hỳt thuc 52 3.2.7 Liờn quan gia nng 25(OH)vitamin D huyt vi s t cp nm 53 3.2.8 Liờn quan gia nng 25(OH)vitamin D huyt vi mc khú th mRC .54 3.2.9 Liờn quan gia nng 25(OH) vitamin D huyt vi cht lng cuc sng (CAT) .55 3.2.10 Liờn quan gia nng 25(OH)vitamin D huyt vi mc tc nghn ng th .56 3.2.11 Liờn quan gia nng 25(OH) vitamin D huyt theo giai on bnh GOLD 2015 .56 3.2.12 Liờn quan nng 25(OH)vitamin D huyt vi mt vi ch s xột nghim mỏu: .57 3.2.13 Liờn quan nng 25(OH)vitamin D huyt vi chc nng hụ hp 57 CHNG 61 BN LUN 61 4.1 c im chung ca i tng nghiờn cu 61 4.1.1 c im v nhõn trc hc 61 4.1.2 Mt s c im lõm sng ca nhúm bnh COPD 63 4.1.3 c im cn lõm sng ca i tng nghiờn cu 67 4.2 Liờn quan gia nng 25(OH)Vitamin D huyt vi mt vi c im lõm sng v cn lõm sng 69 4.2.1 Nng 25(OH)vitamin D huyt v tui 69 4.2.2 Nng 25(OH)vitamin D huyt v BMI 70 4.2.3 Nng 25(OH)vitamin D huyt v thi gian mc bnh 71 4.2.4 Nng 25(OH) vitamin D huyt v tin s hỳt thuc 72 4.2.5 Nng 25(OH)vitamin D huyt v s baonm .73 4.2.6 Nng 25(OH)vitamin D huyt v s t cp 12 thỏng trc 73 4.2.7 Nng 25(OH)vitamin D huyt v mc khú th mRC, im CAT 74 4.2.8 Nng 25(OH)vitamin D huyt v mt vi ch s xột nghim mỏu 76 4.2.9 Nng 25(OH)vitamin D huyt v mc tc nghn ng th 77 4.2.10 Nng 25(OH)vitamin D huyt v giai on bnh theo GOLD 2015 77 KT LUN 79 KIN NGH 80 TI LIU THAM KHO DANH MC BNG Bng 1.1: Phõn loi giai on COPD theo GOLD 2011 .12 Bng 1.2 Chn oỏn mc v iu tr COPD theo giai on bnh thi k n nh [1] 14 Bng 1.3: Cỏc mụ cú cha th th VDR 21 Bng 2.1: B cõu hi CAT (COPD Assessment Test) 37 Bng 3.1 c im v tui, cõn nng, chiu cao, ch s c th 41 Bng 3.2 Phõn b TNC theo ch s c th 42 Bng 3.3 Phõn b TNC theo nhúm tui 42 Bng 3.4 Phõn b i tng nghiờn cu theo tin s t cp 12 thỏng trc 45 Bng 3.5 c im triu chng lõm sng ca nhúm bnh 45 Bng 3.6 c im mt vi xột nghim huyt hc, sinh húa ca nhúm bnh 47 Bng 3.7 Phõn b TNC theo nng 25(OH)vitamin D huyt 48 Bng 3.8 Liờn quan gia nng 25(OH) vitamin D huyt vi tui 48 Bng 3.9 Liờn quan gia nng 25(OH)vitamin D huyt vi BMI 49 Bng 3.10 Liờn quan gia nng 25(OH) vitamin D huyt vi thi gian mc bnh 49 Bng 3.11 Liờn quan gia nng 25(OH)vitamin D huyt vi tin s hỳt thuc 51 Bng 3.12 Liờn quan gia nng 25(OH)vitamin D huyt vi s baonm 51 Bng 3.13 Liờn quan gia nng 25(OH)vitamin D huyt vi thi gian hỳt thuc 52 Bng 3.14 Liờn quan gia nng 25(OH)vitamin D huyt vi s t cp nm .53 77 D3 cựng vi hormone tuyn cn giỏp (PTH) v calcitonin iu chnh nng canxi v pht mỏu PTH c tng cng sn xut ỏp ng vi nng canxi huyt thp v nú gõy vic sn xut 1,25 (OH) D3 4.2.9 Nng 25(OH)vitamin D huyt v mc tc nghn ng th Trong nghiờn cu ca chỳng tụi trung bỡnh nng 25(OH)vitamin D huyt gim dn theo mc tc nghn ng th, s khỏc bit cú ý ngha thng kờ vi p < 0,05 Nng 25(OH)vitamin D huyt tng quan thun: vi %FEV1 ( r=0,417, p =0,001), vi %FEV1/FVC (r= 0,491, p < 0,001) Kt qu nghiờn cu ca chỳng tụi cng tng t nh mt s tỏc gi khỏc: nng 25(OH)vitamin D huyt tng quan thun vi %FEV1 Tỏc gi Louise J.P.P v cng s (2012) [50] Wim J v cng s (2009) [53] Saida A.F v cng s (2015) [70] Chỳng tụi n 433 262 62 r 0,271 0,28 0,61 0,417 p < 0,001 < 0,001 < 0,001 0,001 4.2.10 Nng 25(OH)vitamin D huyt v giai on bnh theo GOLD 2015 Trong nghiờn cu ca chỳng tụi trung bỡnh nng 25(OH)vitamin D huyt ca cỏc nhúm bnh nhõn COPD theo GOLD 2015: nhúm GOLD A: 26,37 8,68 ng/ml, GOLD B: 19,83 6,40 ng/ml, GOLD C: 18,24 6,38 ng/ml, GOLD D: 20,55 8.98 ng/ml Chỳng tụi thy rng cú gim nng 25(OH)vitamin D huyt theo mc nng ca bnh theo GOLD 2015, nhiờn s khỏc v trung bỡnh nng 25(OH)vitamin D huyt gia cỏc nhúm khụng cú ý ngha thng kờ Nghiờn cu ca chỳng tụi khỏc so vi nghiờn cu ca mt s tỏc gi trờn th gii: Balakrishnan M v cng s (2014) [61]: Nghiờn cu trờn 62 bnh nhõn COPD, trung bỡnh nng 25(OH)vitamin D huyt 78 cỏc nhúm l GOLD A (n=15): 41,02 14,12, GOLD B (n=6): 31,51 12,49, GOLD C (n=7): 17,63 8,51, GOLD D (n=34): 16,91 7,89 Nng 25(OH)vitamin D cú tng quan nghch bin vi mc nng ca bnh theo GOLD (r = - 0,406, p < 0,01) Gii thớch s khỏc ny chỳng tụi cho rng ch yu bnh nhõn chỳng tụi chn tham gia nghiờn cu l nhng bnh nhõn t cp ca bnh, mt khỏc vic ỏnh giỏ im mRC, CAT cng ph thuc vo ch quan ngi bnh, nờn cng cú s nh hng n phõn loi giai on bnh theo GOLD 2015 79 KT LUN Qua nghiờn cu nng 25(OH)vitamin D huyt trờn 120 i tng nghiờn cu: ú 62 i tng nghiờn cu mc bnh phi tc nghn mn tớnh v 58 ngi bỡnh thng n khỏm v iu tr ti bnh vin E chỳng tụi cú kt lun sau: Nng 25(OH)vitamin D huyt ca nhúm bnh thp hn nhúm chng cú ý ngha thng kờ vi p < 0,001 - Trung bỡnh nng 25(OH)vitamin D ca nhúm bnh COPD l: 22,808,89 (ng/ml), t l bnh nhõn thiu 25(OH)vitamin D (< 30 ng/ml) l ph bin chim 79%, ú thiu nng chim 40,3%, thiu nh 38,7% - Trung bỡnh nng 25(OH)vitamin D ca nhúm chng l: 29,7110,24 (ng/ml), t l bnh nhõn thiu 25(OH)vitamin D l 55,2% Liờn quan gia nng 25(OH)vitamin D huyt vi mt s yu t lõm sng, cn lõm sng ca bnh nhõn COPD - Nng 25(OH)vitamin D huyt cú mi tng quan nghch vi: thi gian mc bnh (r = - 0,394, p < 0,05), s bao nm (r = - 0,529, p < 0,001), im MRC (vi r = - 0,375, p < 0,05), im CAT (vi r = - 0,344, p < 0,05), s t cp nm ( vi r = - 0,385, p < 0,05) - Nng 25(OH)vitamin D huyt tng quan thun vi %FEV1 (vi r=0,417, p =0,001), %FEV1/FVC (vi r=0,491, p < 0,001) - Nng 25(OH)vitamin D huyt cú mi liờn quan nghch vi thi gian hỳt thuc vi p < 0,05 80 KIN NGH Cn xột nghim nng 25(OH)vitamin D huyt bnh nhõn bnh phi tc nghn mn tớnh v xem xột b xung vitamin D bnh nhõn giai on bnh nng v bnh nhõn cú xột nghim nng 25(OH)vitamin D gim TI LIU THAM KHO Ngụ Quý Chõu (2012) Bnh phi tc nghn mn tớnh, Bnh hc ni khoa 1-NXB Y hc, 42-58 Cantorna M.T, Zhu Y, Froicu M et al (2004) Vitamin D status, 1,25dihydroxyvitamin D3, and the immune system Am J Clin Nutr, 80(6 Suppl) 1717S-20S Lappe J.M, 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measure of health status for chronic airflow limitation The St Georges Respiratory qestionnaire.Am Rev Respir Dis, 145(6): 1321-1327 70 Saida A.F, Abd-Elnaeem E.A (2015) Vitamin D and chronic obstractive pulmonary disease Egyptian journal of chest diseases and tuberculosis 69(1): 67 73 BNH N NGHIấN CU Mó bnh ỏn: HNH CHNH H v tờn: Nm sinh: Gii: Ngh nghip: Dõn tc: a ch: S in thoi: Ngy vo vin: Ngy phng vn: CHUYấN MễN 2.1 Triu chng lõm sng - Lý vo vin: - Bnh ng mc : Cú Khụng Bnh gỡ: - Thi gian xut hin triu chng ln ny (Cỏch ngy vo vin): - Tin s thi gian mc bnh: - Thi gian iu tr corticoid dng xt: Thng xuyờn Khụng thng xuyờn - S t cp 12 thỏng gn õy: - Hỳt thuc lỏ, thuc lo: Cú v ang hỳt Khụng 2.Cú v ó b Hỳt thuc th ng S lng thuc hỳt:(bao - nm) Thi gian hỳt (nm): - Triu chng c nng: Khú th Tc nng ngc Ho Khc m 5.Trng ngc: - Khỏm thc th Mch (ck/ph) Nhit Huyt ỏp mmHg 4.Cõn nng (kg): Chiu cao (m): BMI = Cõn nng(kg)/ Chiu cao2(m) = Du hiu tõm ph mn: cú; khụng Ngún tay dựi trng: cú; khụng Hỡnh dng lng ngc: bỡnh thng; hỡnh thựng Co kộo c hụ hp ph Lng ngc gừ vang 10 RRPN gim 11 Rale: a Rớt; b Ngỏy; c N; d m - B cõu hi mMRC(Medical Research Council): Khú th gng sc mnh Khú th i li nhanh, leo dc Khú th i chm, hoc dng li th i vi ngi cựng tui Dng li th sau i 100 m Khú th thay qun ỏo, khụng th nh ỏnh giỏ khú kh theo b cõu hi mMRC: - B cõu hi CAT(COPD Assessment Test): Tụi hon ton khụng ho Tụi khụng khc m, khụng Tụi ho thng xuyờn Tụi khc nhiu m, cm cú cm giỏc cú m Tụi khụng cú cm giỏc nng giỏc luụn cú m ngc Tụi rt nng ngc ngc Khụng khú th leo dc Rt khú th leo dc hoc hoc cu thang cu thang Tụi khụng bi gii hn lm Tụi b gii hn lm vic vic nh Tụi rt t tin nh nh nhiu Tụi khụng h t tin bt chp bnh phi Tụi ng rt yờn gic nh vỡ bnh phi Tụi ng khụng yờn gic vỡ Tụi cm thy rt khe bnh phi Tụi cm thy khụng cũn chỳt sc lc no o lng tỡnh trng sc khe theo b cõu hi CAT: 2.2 Kt qu cn lõm sng 2.2.1 Cụng thc mỏu: HC (T/L) Hb(g/L) Hct BC(G/L) BCTT/Lympho TC(G/L) Mỏu lng (1h/2h) 2.2.2 Sinh húa mỏu: 25(OH)D (ng/ml) Calci (mmol/l) CRP (mg/dl) 2.2.3 o CNHH: FVC(L) FVC% FEV1(L) FEV1 % FEV1/FVC(%) Chn oỏn: - Giai on COPD theo chc nng thụng khớ: - Phõn nhúm COPD theo GOLD 2015: A B C D - Bnh phi hp: Ngi lm bnh ỏn Trn Anh Sỏng ... GIO DC V O TO B Y T TRNG I HC Y H NI TRN ANH SNG NGHIÊN CứU NồNG Độ VITAMIN D HUYếT THANH BệNH NHÂN BệNH PHổI TắC NGHẽN MạN TíNH Chuyờn ngnh: Ni khoa Mó s: 60720140 LUN VN THC S Y HC Ngi hng dn... Anh Sỏng DANH MC VIT TT 1,25(OH) 2vitamin D: 25(OH )vitamin D: BMI: CAT: MRC: CNHH: COPD: Cs: DBP: TNC: FEV1/FVC: FEV1: FVC: GOLD: 1, 25 dihydroxyvitamin D 25- hydroxyvitamin D Body Mass Index (Ch... v vitamin D/ ngy Vitamin D mỏu s gn vi protein v c chuyn n gan gan, di tỏc dng ca enzym 25-hydroxylase, vitamin D c chuyn thnh 25-hydroxyvitamin D (25(OH )vitamin D) S tng hp 25(OH )vitamin D