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- 1. c Impactul clliinniicc șșii eevvoolluuttiivv aall ccoommoorrbbiiddiittăățțiilloorr aassoocciiaattee îînn BBPPOOCC DDrr.. MMiihhaaii RRooccaa PPrrooff.. DDrr.. TTrraaiiaann MMiihhaaeessccuu
- 2. c Impactul clliinniicc șșii eevvoolluuttiivv aall ccoommoorrbbiiddiittăățțiilloorr aassoocciiaattee îînn BBPPOOCC Investeşte în oameni ! Proiect cofinanţat din Fondul Social European prin Programul Operaţional Sectorial pentru Dezvoltarea Resurselor Umane 2007 – 2013 Axa prioritară 1 „Educaţie şi formare profesională în sprijinul creşterii economice şi dezvoltării societăţii bazate pe cunoaştere” Domeniul major de intervenţie 1.5 „Programe doctorale și post-doctorale în sprijinul cercetării” Titlul proiectului: Parteneriat strategic pentru creșterea calității cercetării științifice din universitățile medicale prin acordarea de burse doctorale și postdoctorale – DocMed.Net_2.0 Contract nr.: POSDRU/159/1.5/S/136893 Beneficiar: Universitatea de Medicină şi Farmacie ”Iuliu Hatieganu” Cluj-Napoca
- 3. i comorbidită Impactul clinic șși evolutiv al comorbiditățțiilloorr aassoocciiaattee îînn BBPPOOCC DDaattee eeppiiddeemmiioollooggiiccee PPaattooggeenniiaa ccoommoorrbbiiddiittăăţţiilloorr îînn BBPPOOCC CCoommoorrbbiiddiittăăţţiillee ccaarrddiioovvaassccuullaarree TTuullbbuurrăărriillee ddee nnuuttrriiţţiiee,, ddiiaabbeettuull zzaahhaarraatt,, ssiinnddrroommuull mmeettaabboolliicc DDiissffuunnccţţiiaa mmuussccuullaattuurriiii sscchheelleettiiccee OOsstteeooppoorroozzaa AAnnxxiieettaatteeaa,, ddeepprreessiiaa şşii ttuullbbuurrăărriillee ddee ssoommnn CCaanncceerruull ppuullmmoonnaarr
- 4. IImmppaaccttuull cclliinniicc șșii eevvoolluuttiivv aall ccoommoorrbbiiddiittăățțiilloorr aassoocciiaattee îînn BBPPOOCC DDaattee eeppiiddeemmiioollooggiiccee PPaattooggeenniiaa ccoommoorrbbiiddiittăăţţiilloorr îînn BBPPOOCC CCoommoorrbbiiddiittăăţţiillee ccaarrddiioovvaassccuullaarree TTuullbbuurrăărriillee ddee nnuuttrriiţţiiee,, ddiiaabbeettuull zzaahhaarraatt,, ssiinnddrroommuull mmeettaabboolliicc DDiissffuunnccţţiiaa mmuussccuullaattuurriiii sscchheelleettiiccee OOsstteeooppoorroozzaa AAnnxxiieettaatteeaa,, ddeepprreessiiaa şşii ttuullbbuurrăărriillee ddee ssoommnn CCaanncceerruull ppuullmmoonnaarr
- 5. BPOC – oo pprroobblleemmăă ddee ssăănnăăttaattee ppuubblliiccăă
- 6. BBPPOOCC –– oo pprroobblleemmăă ddee ssăănnăăttaattee ppuubblliiccăă • PPee ppllaann mmoonnddiiaall –– 221100 mmiilliiooaannee ddee bboollnnaavvii şşii 33 mmiilliiooaannee ddee ddeecceessee aannuuaall ((55%% ddiinn mmoorrttaalliittaatteeaa gglloobbaallăă))11 • PPrreevvaalleennţţăă îînn ccoonnttiinnuuăă ccrreeşştteerree:: aa 66--aa ccaauuzzăă ddee mmoorrttaalliittaattee llaa nniivveell mmoonnddiiaall îînn 11999900,, eessttiimmaattiivv -- aa 33--aa ccaauuzzăă îînn 2200220022 11..WWoorrlldd HHeeaalltthh OOrrggaanniizzaattiioonn.. WWoorrlldd HHeeaalltthh RReeppoorrtt 22000044.. SSttaattiissttiiccaall AAnnnneexx -- ttaabbllee 22 aanndd 33:: 112200--113311 22.. MMuurrrraayy CCJJ.. LLaanncceett 11999977 ;; 334499((99006644)):: 11449988--550044..
- 9. Comorbidităţile diagnosticate îînn ssppiittaall llaa ppaacciieennţţiiii ccuu BBPPOOCC UUSSAA NNaattiioonnaall HHoossppiittaall DDiisscchhaarrggee SSuurrvveeyy –– iinncclluuddee 4477 mmiill iinntteerrnnăărrii ppeennttrruu BBPPOOCC ((88,,55%%)) îînn UUSSAA,, ppeerriiooaaddaa 11997799--22000011 Holguin F, et al. Chest 2005;128(4):2005-11.
- 10. Cauzele mortalităţii la pacienţii iinntteerrnnaaţţii ccuu BBPPOOCC UUSSAA NNaattiioonnaall HHoossppiittaall DDiisscchhaarrggee SSuurrvveeyy –– iinncclluuddee 4477 mmiill iinntteerrnnăărrii ppeennttrruu BBPPOOCC ((88,,55%%)) îînn UUSSAA,, ppeerriiooaaddaa 11997799--22000011 Holguin F, et al. Chest 2005;128(4):2005-11.
- 11. Impactul comorbidităţilor aassuupprraa pprrooggnnoossttiiccuulluuii Men Survival (%) Fjellanger et al, Tidsskr Nor Lægeforen 2003 Women Survival (%) 100 80 60 40 0 6 12 18 24 30 Follow-up (months) 1+ comorbidities No comorbidities 100 80 60 40 0 6 12 18 24 30 Follow-up (months) 1+ comorbidities No comorbidities BBPPOOCC MMoorrttaalliittaatteeaa dduuppăă iinntteerrnnăărrii ddeetteerrmmiinnaattee ddee eexxaacceerrbbăărrii aallee BBPPOOCC::
- 12. IImmppaaccttuull cclliinniicc șșii eevvoolluuttiivv aall ccoommoorrbbiiddiittăățțiilloorr aassoocciiaattee îînn BBPPOOCC DDaattee eeppiiddeemmiioollooggiiccee PPaattooggeenniiaa ccoommoorrbbiiddiittăăţţiilloorr îînn BBPPOOCC CCoommoorrbbiiddiittăăţţiillee ccaarrddiioovvaassccuullaarree TTuullbbuurrăărriillee ddee nnuuttrriiţţiiee,, ddiiaabbeettuull zzaahhaarraatt,, ssiinnddrroommuull mmeettaabboolliicc DDiissffuunnccţţiiaa mmuussccuullaattuurriiii sscchheelleettiiccee OOsstteeooppoorroozzaa AAnnxxiieettaatteeaa,, ddeepprreessiiaa şşii ttuullbbuurrăărriillee ddee ssoommnn CCaanncceerruull ppuullmmoonnaarr
- 13. CCXXCCLL 99,, 1100,, 1111 CCXXCCLL 11,, 88 CCCCLL 22 PPrrootteeaazzee TTGFF -- ββ PPrroocceessuull iinnffllaammaattoorr îînn BBPPOOCC EEmmffiizzeemm ppuullmmoonnaarr HHiippeerrsseeccrreeţţiiee mmuuccuuss FFiibbrroozzaa ccăăii aaeerriieennee mmiiccii
- 14. Inflamaţia sistemică şşii ccoommoorrbbiiddiittăăţţiillee BBPPOOCC Fabbri LM, et al. Eur Respir J 2008;31(1):204-12.
- 15. IImmppaaccttuull cclliinniicc șșii eevvoolluuttiivv aall ccoommoorrbbiiddiittăățțiilloorr aassoocciiaattee îînn BBPPOOCC DDaattee eeppiiddeemmiioollooggiiccee PPaattooggeenniiaa ccoommoorrbbiiddiittăăţţiilloorr îînn BBPPOOCC CCoommoorrbbiiddiittăăţţiillee ccaarrddiioovvaassccuullaarree TTuullbbuurrăărriillee ddee nnuuttrriiţţiiee,, ddiiaabbeettuull zzaahhaarraatt,, ssiinnddrroommuull mmeettaabboolliicc DDiissffuunnccţţiiaa mmuussccuullaattuurriiii sscchheelleettiiccee OOsstteeooppoorroozzaa AAnnxxiieettaatteeaa,, ddeepprreessiiaa şşii ttuullbbuurrăărriillee ddee ssoommnn CCaanncceerruull ppuullmmoonnaarr
- 16. BBPPOOCC şşii ffaaccttoorriiii ddee rriisscc ccaarrddiioovvaassccuullaarrii MMooddiiffiiccaarreeaa rriiggiiddiittăăţţiiii ppeerreetteelluuii aarrtteerriiaall •AAffeeccttaarreeaa ffuunnccţţiieeii rreessppiirraattoorriiii ((VVEEMMSS) ssee aassoocciiaazzăă iinnddeeppeennddeenntt ccuu ccrreeşştteerreeaa rriiggiiddiittăăţţiiii aarrtteerriiaallee,, eessttiimmaattăă pprriinn vviitteezzaa uunnddeeii ddee ppuullss ((PPWWVV).. •MMooddeell ddee aannaalliizzăă aajjuussttaatt ppeennttrruu vvâârrssttăă,, îînnăăllţţiimmee,, ggrreeuuttaattee,, ffuummaatt,, hhiippeerrccoolleesstteerroolleemmiiee,, ddiiaabbeett zzaahhaarraatt ((pp << 00,,000011):: ↑↑PPWWVV ((22,,55mm//ss) ↓↓VVEEMMSS ((119955,,22 ±± 5500,,11mmll) Zureik M et al. Am J Respir Crit CareMed 2001;164:2181–2185
- 17. BBPPOOCC şşii ffaaccttoorriiii ddee rriisscc ccaarrddiioovvaassccuullaarrii Modificarea rigidităţii ppeerreetteelluuii aarrtteerriiaall •IILL--66 ssee ccoorreelleeaazzăă PPWWVV aaoorrttiiccăă (( rr == 00,,3311,, pp << 00,,00000011) Sabit R et al. Am J Respir Crit Care Med 2007;175:1259–1265
- 18. BBPPOOCC şşii ffaaccttoorriiii ddee rriisscc ccaarrddiioovvaassccuullaarrii Modificarea rigidităţii ppeerreetteelluuii aarrtteerriiaall •SSeevveerriittaatteeaa eemmffiizzeemmuulluuii –– pprreeddiiccttoorr iinnddeeppeennddeenntt ppeennttrruu rriiggiiddiittaatteeaa aarrtteerriiaallăă ((PPWWMM) ((rr==00,,447711,, PP<<00,,000011) McAllister DA et al. Am J Respir Crit Care Med 2007;176(12):1208-1214.
- 19. BBPPOOCC şşii ffaaccttoorriiii ddee rriisscc ccaarrddiioovvaassccuullaarrii Afectarea reactivităţii vvaassccuullaarree PPrreeddiiccttoorrii rreeaaccttiivviittaattee vvaassccuullaarrăă BBPPOOCC MMaarrkkeerrii iinnffllaammaattiiee:: CCRRPP VVaassooddiillaattaaţţiiaa mmeeddiiaattăă ddee fflluuxx FFuunnccţţiiaa rreessppiirraattoorriiee:: VVEEMMSS Eickhoff Pet al. Am J Respir Crit Care Med 2008;178(12):1211-8
- 20. BBPPOOCC şşii hhiippeerrtteennssiiuunneeaa aarrtteerriiaallăă RRiissccuull ddee HTTAA îînn ffuunnccţţiiee ddee ssttaaddiiuull BBPPOOCC ((GGOOLLDD) • AAtthheerroosscclleerroossiiss RRiisskk iinn CCoommmmuunniittiieess SSttuuddyy ((AARRIICC)) şşii CCaarrddiioovvaassccuullaarr HHeeaalltthh SSttuuddyy ((CCHHSS)) -- 2200229966 ssuubbiieeccţţii,, >>4455 aannii PPrroocceenntt GOLD 3 GOLD 2 GOLD 1 Restricted GOLD 0 Normal Mannino DM et al. Eur Respir J 2008;32(4):962-9 60 50 40 30 20 10 0
- 21. BBPPOOCC şşii iinnssuuffiicciieennţţaa ccaarrddiiaaccăă BB--ttyyppee nnaattrriiuurreettiicc ppeeppttiiddeess ((BBNNPP,, NNTT--pprrooBBNNPP)) –– ddiiaaggnnoossttiiccaarreeaa ddiissffuunnccţţiieeii ssiissttoolliiccee llaa ppaacciieennţţiiii iinntteerrnnaaţţii ccuu eexxaacceerrbbăărrii aallee BBPPOOCC:: •BBNNPP << 110000 ppgg//mmll:: SSnn==9922%%,, VVPP--==9911%% •BBNNPP >> 550000 ppgg//mmll:: SSnn==8800%%,, VVPP++==4477%% •IIssttoorriiccuull ddee bbooaallăă ccoorroonnaarriiaannăă aassoocciiaatt ccuu BBNNPP>>550000ppgg//mmll –– pprreeddiiccttoorr iinnddeeppeennddeenntt aall aaffeeccttăărriiii ffuunnccţţiieeii ssiissttoolliiccee aa vveennttrriiccuulluulluuii ssttâânngg.. Gariani K, et al. Swiss Med Wkly 2011;141:w13298.
- 22. BBPPOOCC şşii iinnssuuffiicciieennţţaa ccaarrddiiaaccăă NNTT--pprrooBBNNPP –– rrooll pprrooggnnoossttiicc îînn eexxaacceerrbbăărriillee bboolliiii ppuullmmoonnaarree ccrroonniiccee • ↑↑ NNTT--pprrooBBNNPP >> 558877..99 ppgg//mmll :: ↑↑MMoorrttaalliittaatteeaa llaa uunn aann ((OORR==33,,9900;; 9955%% IICC 11,,4466––1100,,4477;; pp==00,,000066)) Medina AM, et al. Eur J Intern Med 2011;22(2):167-71.
- 23. BBPPOOCC şşii iinnssuuffiicciieennţţaa ccaarrddiiaaccăă Emfizemului pulmonar şi gradul obstrucţiei bbrroonnşşiiccee ssee ccoorreelleezzăă lliinniiaarr ccuu aaffeeccttaarreeaa ffuunnccţţiieeii vveennttrriiccuullaarree ssttâânnggii:: ↑↑1100%% EEmmffiizzeemm ↓↓44,,11mmll VVTTDDVVSS ↓↓22,,77mmll VVSS ↓↓00,,1199 ll//mmiinn DDCC ↓↓1100%% VVEEMMSS//FFVVCC ↓↓11,,77mmll VVTTDDVVSS ↓↓11,,55mmll VVSS ↓↓00,,11 ll//mmiinn DDCC Barr RG et al. N Engl J Med 2010;362:217–227.
- 24. MMaannaaggeemmeennttuull BBPPOOCC llaa ppaacciieennţţiiii ccuu ccoommoorrbbiiddiittăăţţii DDaattee eeppiiddeemmiioollooggiiccee PPaattooggeenniiaa ccoommoorrbbiiddiittăăţţiilloorr îînn BBPPOOCC CCoommoorrbbiiddiittăăţţiillee ccaarrddiioovvaassccuullaarree TTuullbbuurrăărriillee ddee nnuuttrriiţţiiee,, ddiiaabbeettuull zzaahhaarraatt,, ssiinnddrroommuull mmeettaabboolliicc DDiissffuunnccţţiiaa mmuussccuullaattuurriiii sscchheelleettiiccee OOsstteeooppoorroozzaa AAnnxxiieettaatteeaa,, ddeepprreessiiaa şşii ttuullbbuurrăărriillee ddee ssoommnn CCaanncceerruull ppuullmmoonnaarr
- 25. CCaaşşeexxiiaa llaa ppaacciieennţţiiii ccuu BBPPOOCC • FFaatt--ffrreeee bbooddyy mmaassss iinnddeexx:: <<1177 kkgg//mm22 ((mm),, <<1144 kkgg//mm22 ((ff) • PPrreevvaalleennţţaa:: 2200 –– 4400%% îînn BBPPOOCC • MMeeccaanniissmmee ppaattooggeenniiccee:: • DDeezzeecchhiilliibbrruu eenneerrggeettiicc ((↑↑ccoosstt OO22 eexxeerrcciiţţiiuu ffiizziicc,, ↑↑lluuccrruull mmuussccuullaattuurriiii rreessppiirraattoorriiii) • AAttrrooffiiee pprriinn iinnaaccttiivviittaattee ffiizziiccăă şşii aaffeeccttaarreeaa mmuussccuullaarrăă ((iinneeffiicciieennţţăă eenneerrggeettiiccăă) • Hiippooxxiiee ttiissuullaarrăă ddaattoorriittăă hhiippooxxeemmiieeii • IInnffllaammaaţţiiee ssiisstteemmiiccăă ((TTNFF--αα,, IILL--11ββ,, IILL--66,, CCRRPP,, RROOSS) • DDeeffiicciieennţţăă hhoorrmmoonnii aannaabboolliizzaannţţii ((tteessttoosstteerroonn,, GGFF şşii aanndd iinnssuulliinn--lliikkee ggrroowwtthh ffaaccttoorr) Wagner PD. Eur Respir J 2008;31(3):492-501
- 26. CCaaşşeexxiiaa llaa ppaacciieennţţiiii ccuu BBPPOOCC Masa corporală – factor de risc ppeennttrruu mmoorrttaalliittaattee:: CCooppeennhhaaggeenn CCiittyy HHeeaarrtt SSttuuddyy:: 22113322 ppaacciieennţţii ccuu VVEEMMSS//CCVVFF<<00,,77,, 1177 aannii ffoollllooww--uupp:: BBMMII << 2211kkgg//mm22 aassoocciiaazzăă RRRR 77..1111 [[9955%% CCII 22..9977--1177..0055]] ppeennttrruu mmoorrttaalliittaattee ddaattoorraattăă BBPPOOCC Landbo C, et al. Am J Respir Crit Care Med 1999;160(6):1856-61.
- 27. CCaaşşeexxiiaa llaa ppaacciieennţţiiii ccuu BBPPOOCC SSuusscceeppttiibbiilliittaattee ggeenneettiiccăă llaa ccaaşşeexxiiee îînn BBPPOOCC:: SSNPP --551111 îînn ggeennaa IILL--11ββ:: ggeeoottiippuurriillee CCCC--aassoocciiaatt ccuu ccaaşşeexxiiaa,, TTTT--pprrootteeccttiivv,, CCTT--rriisscc iinntteerrmmeeddiiaarr Wagner PD. Eur Respir J 2008;31(3):492-501
- 28. CCaaşşeexxiiaa llaa ppaacciieennţţiiii ccuu BBPPOOCC PPllaassmmaa GGrreelliinn lleevveell -- eennddooggeennoouuss GGHH--rreelleeaassiinngg ppeeppttiiddee:: IInntteerrvviinnee îînn sseennss ppoozziittiivv îînn eecchhiilliibbrruull eenneerrggeettiicc:: ↓↓uuttiillzzaarreeaa ggrrăăssiimmiiii şşii ccrreeşşttee aappoorrttuull aalliimmeennttaarr ((eeffeecctt aannaabboolliizzaanntt).. ÎÎnn BBPPOOCC :: • GGrreelliinnaa ppllaassmmaattiiccăă ssee ccoorreelleeaazzăă nneeggaattiivv ccuu BBMMII şşii ppoozziittiivv ccuu ffaaccttoorriiii ccaattaabboolliizzaannţţii ((TTNFFαα,, nnoorreeppiinneeffrriinnăă,, IILL66) • GGrreelliinnaa ssee ccoorreelleeaazzăă ppoozziittiivv ccuu vvoolluummuull rreezziidduuaall şşii VVRR//CCPPTT Itoh T, et al. Am J Respir Crit Care Med 2004; 170: 879–882
- 29. BBPPOOCC şşii ddiiaabbeettuull zzaahhaarraatt RRiisscc ddee aappaarriiţţiiee aa ddiiaabbeettuulluuii zzaahhaarraatt ttiipp 22 • NNuurrsseess’’ HHeeaalltthh SSttuuddyy –– ssttuuddiiuu pprroossppeeccttiivv ddee ccoohhoorrttăă iinncclluuzzâânndd 110033661144 ffeemmeeii,, eevvaalluuaattee bbii--aannuuaall îînn ppeerriiooaaddaa 11998888––11999966,, ppeennttrruu BBPPOOCC,, aassttmm bbrroonnşşiicc,, ddiiaabbeett zzaahhaarraatt Rana JS et al. Diabetes Care 2004;27(10):2478-84
- 30. BBPPOOCC şşii ddiiaabbeettuull zzaahhaarraatt RRiisscc DDZZ îînn ffuunnccţţiiee ddee ssttaaddiiuull BBPPOOCC ((GGOOLLDD)) • AAtthheerroosscclleerroossiiss RRiisskk iinn CCoommmmuunniittiieess SSttuuddyy ((AARRIICC)) şşii CCaarrddiioovvaassccuullaarr HHeeaalltthh SSttuuddyy ((CCHHSS)) -- 2200229966 ssuubbiieeccţţii,, >>4455 aannii PPrroocceenntt 25 20 15 10 5 0 GOLD 3 GOLD 2 GOLD 1 Restricted GOLD 0 Normal Mannino DN et al. Eur Respir J 2008;32(4):962-9
- 31. BBPPOOCC şşii ssiinnddrroommuull mmeettaabboolliicc IInntteerrnnaattiioonnaall DDiiaabbeetteess FFeeddeerraattiioonn ((IIDDFF)) FFaaccttoorr oobblliiggaattoorr OObbeezziittaattee cceennttrraallăă CCiirrccuummffeerriinnţţaa ttaalliieeii ≥≥ 9944ccmm llaa bbăărrbbaaţţii şşii ≥≥ 8800ccmm llaa ffeemmeeii PPlluuss oorriiccaarree ddooii ddiinn uurrmmăăttoorriiii ffaaccttoorrii VVaallooaarreeaa ccrreessccuuttăă aa ttrriigglliicceerriiddeelloorr ≥≥ 115500 mmgg//ddLL ((11..77 mmmmooll//LL))** HHDDLL--ccoolleesstteerrooll ssccăăzzuutt << 4400 mmgg//ddLL llaa bbăărrbbaaţţii şşii << 5500 mmgg//ddLL llaa ffeemmeeii** HHiippeerrtteennssiiuunnee aarrtteerriiaallăă TTAA ssiissttoolliiccăă ≥≥ 113300 ssaauu TTAA ddiiaassttoolliiccăă ≥≥ 8855 mmmm HHgg** hhiippeerrgglliicceemmiiee ≥≥ 110000 mmgg//ddLL ((55..66 mmmmooll//LL))** ** SSaauu ttrraattaammeenntt ssppeecciiffiicc http://www.idf.org/webdata/docs/MetS_def_update2006.pdf
- 32. BBPPOOCC şşii ssiinnddrroommuull mmeettaabboolliicc 4433%% ddiinnttrree ppaacciieennţţiiii ccuu BBPPOOCC şşii 2211%% ddiinn ssuubbiieeccţţiiii ccoonnttrrooll aauu pprreezzeennttaatt 33 ssaauu mmaaii mmuullttee ccaarraacctteerriissttiiccii ddeetteerrmmiinnaannttee ppeennttrruu ssiinnddrroommuull mmeettaabboolliicc.. Marquis K et al. J Cardiopulm Rehabil 2005;25(4):226-32.
- 33. BBPPOOCC şşii ssiinnddrroommuull mmeettaabboolliicc PPrrooffiilluull mmeettaabboolliicc şşii iinnffllaammaattoorr aall ppaacciieennttuulluuii oobbeezz ccuu BBPPOOCC • OObbeezziittaatteeaa aassoocciiaazzăă mmooddiiffiiccăărrii iinnffllaammaattoorriiii şşii mmeettaabboolliiccee Poulain M et al. Chron Respir Dis. 2008;5(1):35-41.
- 34. IImmppaaccttuull cclliinniicc șșii eevvoolluuttiivv aall ccoommoorrbbiiddiittăățțiilloorr aassoocciiaattee îînn BBPPOOCC DDaattee eeppiiddeemmiioollooggiiccee PPaattooggeenniiaa ccoommoorrbbiiddiittăăţţiilloorr îînn BBPPOOCC CCoommoorrbbiiddiittăăţţiillee ccaarrddiioovvaassccuullaarree TTuullbbuurrăărriillee ddee nnuuttrriiţţiiee,, ddiiaabbeettuull zzaahhaarraatt,, ssiinnddrroommuull mmeettaabboolliicc DDiissffuunnccţţiiaa mmuussccuullaattuurriiii sscchheelleettiiccee OOsstteeooppoorroozzaa AAnnxxiieettaatteeaa,, ddeepprreessiiaa şşii ttuullbbuurrăărriillee ddee ssoommnn CCaanncceerruull ppuullmmoonnaarr
- 35. Disfuncţia mmuussccuullaattuurriiii sscchheelleettiiccee îînn BBPPOOCC AAffeeccttaarreeaa mmuuşşcchhiiuulluuii ccvvaaddrriicceeppss îînn BBPPOOCC:: CClliinniicc ↓↓FFoorrţţaa mmuussccuullaarrăă ↑↑FFaattiiggaabbiilliittaatteeaa şşii dduurraattaa ddee rreeccuuppeerraarree dduuppăă eeffoorrtt ↓↓AAnndduurraannţţaa mmuussccuullaarrăă ↓↓AArriiaa sseeccţţiiuunniiii mmuussccuullaarree ttrraannssvveerrssaallee SSttrruuccttuurraall ↓↓PPrrooppoorrţţiieeii ffiibbrreelloorr mmuussccuullaarree ddee ttiipp II ↑↑PPrrooppoorrţţiieeii ffiibbrreelloorr mmuussccuullaarree ddee ttiipp IIIIxx ↓↓AArriiaa sseeccţţiiuunniiii ttrraannssvveerrssaallee aa ffiibbrreeii ↓↓SSuupprraaffeeţţeeii ddee ccoonnttaacctt aa ccaappiillaarreelloorr ccuu ffiibbrreellee mm.. MMeettaabboolliicc ↓↓CCaappaacciittaatteeaa eennzziimmaattiiccăă ooxxiiddaattiivvăă ↑↑CCaappaacciittaatteeaa eennzziimmaattiiccăă gglliiccoolliittiiccăă ↑↑AAcciidd llaaccttiicc ccuu aacciiddoozzăă iinnttrraacceelluullaarrăă ↓↓FFoossffooccrreeaattiinnăă// ffoossffaatt aannoorrgg.. –– mmaarrkkeerr eenneerrggeettiicc mmuussccuullaarr Man WD. Clin Sci 2009;117(7):251-64.
- 36. Disfuncţia mmuussccuullaattuurriiii sscchheelleettiiccee îînn BBPPOOCC PPaattooggeenniiaa aaffeeccttăărriiii mmuussccuullaarree sscchheelleettiiccee îînn BBPPOOCC Man WD. Clin Sci 2009;117(7):251-64.
- 37. DDiissffuunnccţţiiaa mmuussccuullaattuurriiii sscchheelleettiiccee îînn BBPPOOCC FFoorrţţaa mmuussccuullaarrăă ccvvaaddrriicceeppss –– pprreeddiiccttoorr mmoorrttaalliiaattaattee îînn BBPPOOCC • QQMMVVCC ((HHRR 00..9911 ((9955%% CCII 00..8833 ttoo 00..9999));; pp == 00..003366)) • QQMMVVCC –– pprreeddiiccttoorr eevvoolluuttiivv mmaaii vvaalloorrooss ddeeccââtt vvâârrssttaa,, BBMMII,, VVEEMMSS Swallow EB et al. Thorax 2007;62(2):115-20.
- 38. AAccttiivviittaatteeaa ffiizziiccăă îînn BBPPOOCC Studiu cohortă 170 subiecţi cu BPOC –– eevvaalluuaarree nniivveell aaccttiivviittaattee ffiizziiccăă ((iinnddiiccee PPAALL)) pprriinn mmuullttiisseennssoorryy aarrmmbbaanndd oo ppeerriiooaaddăă ddee 1100--5533 lluunnii,, mmoorrttaalliittaattee 1155,,44%% -- pprreeddiiccttoorrii:: •AAccttiivviittaatteeaa ffiizziiccăă –– cceell mmaaii ppuutteerrnniicc pprreeddiiccttoorr aall mmoorrttaalliittăăţţiiii ddee oorriiccee ccaauuzzăă îînn BBPPOOCC:: ↑↑00,,1144 PPAALL:: HHRR 00,,4466;; 9955%% CCII,, 00,,3333--00,,6644;; PP << ..000011 •FFuunnccţţiiaa vveennttrriiccuullaarrăă ((TTeeii--iinnddeexx)) ((HHRR,, 11,,2266;; 9955%% CCII,, 11,,0044--11,,5544;; PP == ..002200)),, •AAddiippoonneeccttiinnaa ((HHRR,, 11,,3344;; 9955%% CCII,, 11,,0066--11,,7711;; PP == ..001177)) •LLeeppttiinnaa ((HHRR,, 00,,8811;; 9955%% CCII,, 00,,6655--00,,9999;; PP == ..004422)),, Waschki B et al. Chest 2011;140(2):331-42.
- 39. AAccttiivviittaatteeaa ffiizziiccăă îînn BBPPOOCC Reabilitarea ppuullmmoonnaarrăă –– aannttrreennaammeennttuull ffiizziicc • ↑↑TToolleerraannţţaa llaa eeffoorrtt • ↓↓DDiissppnneeeeaa • ↑↑CCaalliittaatteeaa vviieeţţiiii • ↑↑FFuunnccţţiiaa aaeerroobbăă aa cceelluulleeii mmuussccuullaarree • ↓↓HHiippeerriinnffllaaţţiiaa ddiinnaammiiccăă • NNUU îîmmbbuunnăăttăăţţeeşşttee ppaarraammeettrriiii ffuunnccţţiioonnaallii rreessppiirraattoorrii Casaburi R et al. N Engl J Med 2009;360(13):1329-35.
- 40. IImmppaaccttuull cclliinniicc șșii eevvoolluuttiivv aall ccoommoorrbbiiddiittăățțiilloorr aassoocciiaattee îînn BBPPOOCC DDaattee eeppiiddeemmiioollooggiiccee PPaattooggeenniiaa ccoommoorrbbiiddiittăăţţiilloorr îînn BBPPOOCC CCoommoorrbbiiddiittăăţţiillee ccaarrddiioovvaassccuullaarree TTuullbbuurrăărriillee ddee nnuuttrriiţţiiee,, ddiiaabbeettuull zzaahhaarraatt,, ssiinnddrroommuull mmeettaabboolliicc DDiissffuunnccţţiiaa mmuussccuullaattuurriiii sscchheelleettiiccee OOsstteeooppoorroozzaa AAnnxxiieettaatteeaa,, ddeepprreessiiaa şşii ttuullbbuurrăărriillee ddee ssoommnn CCaanncceerruull ppuullmmoonnaarr
- 41. OOsstteeooppoorroozzaa –– ccoommoorrbbiiddiittaattee îînn BBPPOOCC FFaaccttoorrii ddee rriisscc:: • FFuummaattuull11 –– >>2200PPAA ddeetteerrmmiinnăă ↓↓BBMMDD lloommbbaarrăă ccuu 1122%% –– ↑↑RRiisscc ffrraaccttuurrii ((xx 22,,33 vveerrtteebbrraallee,, xx11,,77 şşoolldd)) • IInnddiicceellee ddee mmaassăă ccoorrppoorraallăă:: BBMMII ~~ BBMMDD ((rr == 00..3344;; pp << 00..0055))22 –– PPrreeddiiccttoorr oosstteeooppoorroozzăă:: BBMMII << 2222 –– OORR 44..1188 ((9955%% CCII,, 11..1199 ttoo 1144..7711))33 • RReedduucceerreeaa mmaasseeii şşii aa ffoorrţţeeii mmuussccuullaattuurriiii sscchheelleettiiccee • TTeerraappiiaa ccuu gglluuccooccoorrttiiccooiizzii –– hhiippeerrppaarraattiirrooiiddiissmm sseeccuunnddaarr 1. Biskobing DM. Chest 2002; 121: 609–620. 2. Iqbal F et al. Chest 1999; 116:1616–1624 3. Incalzi RA et al. Respir Med 2000; 94:1079–1084
- 42. OOsstteeooppoorroozzaa –– ccoommoorrbbiiddiittaattee îînn BBPPOOCC FFaaccttoorrii ddee rriisscc:: • IInnffllaammaaţţiiaa ssiisstteemmiiccăă ddiinn BBPPOOCC BBPPOOCC TTNNFF αα IILL 11 αα IILL 66 OOSSTTEEOOLLIIZZĂĂ FFOORRMMAARREE OOSSTTEEOOCCLLAASSTTEE • DDeeffiicciittuull ddee vviittaammiinnaa DD ddiinn BBPPOOCC –– nniivveell sseerriicc 2255--OOHH--vviitt..DD mmaaii rreedduuss ddeeccââtt llaa ssuubbiieeccţţiiii ssăănnăăttooşşii Ionescu AA, Schoon E. Eur Respir J Suppl 2003;46:64-75. Shane E et al. Am J Med 1996; 101:262–269.
- 43. OOsstteeooppoorroozzaa –– ccoommoorrbbiiddiittaattee îînn BBPPOOCC DDeeffiicciittuull ddee vviittaammiinnaa DD îînn BBPPOOCC:: • 2255--OOHH--DD ccoorreellaaţţiiee ~~ VVEEMMSS ((rr==00..2288,, pp<<00..00000011)) • AAlleellaa rrss77004411 ((hhoommoozziiggooţţii)) ■ ↓↓2255%% 2255--OOHH--DD ((pp<<00..00000011)) ■ FFaaccttoorr ddee rriisscc BBPPOOCC ((OORR 22..1111;; 9955%% CCII 11..2200 ttoo 33..7711;; pp==00..000099)).. Janssens W, et al. Thorax 2010;65(3):215-20.
- 44. IImmppaaccttuull cclliinniicc șșii eevvoolluuttiivv aall ccoommoorrbbiiddiittăățțiilloorr aassoocciiaattee îînn BBPPOOCC DDaattee eeppiiddeemmiioollooggiiccee PPaattooggeenniiaa ccoommoorrbbiiddiittăăţţiilloorr îînn BBPPOOCC CCoommoorrbbiiddiittăăţţiillee ccaarrddiioovvaassccuullaarree TTuullbbuurrăărriillee ddee nnuuttrriiţţiiee,, ddiiaabbeettuull zzaahhaarraatt,, ssiinnddrroommuull mmeettaabboolliicc DDiissffuunnccţţiiaa mmuussccuullaattuurriiii sscchheelleettiiccee OOsstteeooppoorroozzaa AAnnxxiieettaatteeaa,, ddeepprreessiiaa şşii ttuullbbuurrăărriillee ddee ssoommnn CCaanncceerruull ppuullmmoonnaarr
- 45. AAnnxxiieettaatteeaa şşii ddeepprreessiiaa llaa ppaacciieennttuull ccuu BBPPOOCC DDeepprreessiiaa –– pprreeddiiccttoorr aall rreedduucceerriiii ccaappaacciittăăţţiiii ddee eeffoorrtt îînn BBPPOOCC CCeennttrree ffoorr EEppiiddeemmiioollooggiicc SSttuuddiieess DDeepprreessssiioonn SSccaallee ((CCEESS--DD)) şşii BBrriieeff AAsssseessssmmeenntt SScchheedduullee DDeepprreessssiioonn CCaarrddss ((BBAASSDDEECC)),, 112222 ppaacciieennţţii ccuu BBPPOOCC:: • PPrreevvaalleennţţaa ddeepprreessiieeii:: 2211%% rreessppeeccttiivv 1177%% • CCoorreellaaţţiiaa BBAASSDDEECC şşii CCEESS--DD ccuu:: 66MMWWTT (( rr==00..3333 rreessppeeccttiivv rr==00..44,, pp << 00..000011)) BBOODDEE ((rr == 00..3355,, pp << 00..000011 rreessppeeccttiivv rr == 00..2222,, pp == 00..001166)) • SSccoorruurriillee ddee ddeepprreessiiee nnuu ssee ccoorreelleeaazzăă ccuu VVEEMMSS Al-Shair K et al. Respir Med. 2009;103(10):1572-9. .
- 46. AAnnxxiieettaatteeaa şşii ddeepprreessiiaa llaa ppaacciieennttuull ccuu BBPPOOCC IInncciiddeennţţaa aannxxiieettăăţţiiii//ddeepprreessiieeii ssee ccoorreelleeaazzăă ccuu eeşşeeccuull ttrraattaammeennttuulluuii îînn uurrggeennţţăă aall BBPPOOCC FFaarraa aannxxiieettaattee//ddeepprreessiiee AAnnxxiieettaattee // ddeepprreessiiee p<0.05 0 5 10 15 20 25 Dahlen et al. Chest 2002;122(5):1633-7. . PPeerriiooaaddaa,, zziillee 100 80 60 40 20 0 %% ppaacciieennţţii ccuu eeşşeecc aall ttrraattaammeennttuulluuii BBPPOOCC
- 47. IImmppaaccttuull cclliinniicc șșii eevvoolluuttiivv aall ccoommoorrbbiiddiittăățțiilloorr aassoocciiaattee îînn BBPPOOCC DDaattee eeppiiddeemmiioollooggiiccee PPaattooggeenniiaa ccoommoorrbbiiddiittăăţţiilloorr îînn BBPPOOCC CCoommoorrbbiiddiittăăţţiillee ccaarrddiioovvaassccuullaarree TTuullbbuurrăărriillee ddee nnuuttrriiţţiiee,, ddiiaabbeettuull zzaahhaarraatt,, ssiinnddrroommuull mmeettaabboolliicc DDiissffuunnccţţiiaa mmuussccuullaattuurriiii sscchheelleettiiccee OOsstteeooppoorroozzaa AAnnxxiieettaatteeaa,, ddeepprreessiiaa şşii ttuullbbuurrăărriillee ddee ssoommnn CCaanncceerruull ppuullmmoonnaarr
- 48. CCaanncceerruull ppuullmmoonnaarr llaa ppaacciieennţţiiii ccuu BBPPOOCC FFaaccttoorriiii ddee rriisscc ppeennttrruu ccaanncceerruull ppuullmmoonnaarr îînn BBPPOOCC 22550077 PPaacciieennţţii ccuu BBPPOOCC,, ffuummăăttoorrii,, uurrmmăărriiţţii ppeennttrruu 6600 ddee lluunnii:: 221155 ccaazzuurrii ddee ccaanncceerr ppuullmmoonnaarr ((iinncciiddeennţţăă 1166,,77 ccaazzuurrii//11000000 ppeerrssooaannee//aann)):: de Torres JP, et al. Am J Respir Crit Care Med 2011;184(8):913-9.
- 49. RRiissccuull ddee ccaanncceerr ppuullmmoonnaarr îînn BBPPOOCC RRRR ccaanncceerr ppuullmmoonnaarr:: • 22..0044 ((9955%% CCII:: 11..7722,, 22..4411)) eemmffiizzeemm ppuullmmoonnaarr,, • 11..5522 ((9955%%CCII:: 11..2255,, 11..8844)) bbrroonnssiittăă ccrroonniiccăă,, • 22..2222 ((9955%% CCII:: 11..6666,, 22..9977)) BBPPOOCC.. BBrreennnneerr DDRR,, eett aall.. PPLLooSS OONNEE 22001111;;66:: ee1177447799..
- 50. BPOC şi cancerul pulmonar –– lleeggăăttuurrii ppaattooggeenniiccee AAddccoocckk IIMM,, eett aall.. RReessppiirraattiioonn 22001111;;8811::226655––228844..
- 51. RRoolluull ssttrreessuulluuii ooxxiiddaattiivv ddiinn BBPPOOCC iinn ccaarrcciinnooggeenneezzaa SSTTRREESS OOXXIIDDAATTIIVV ↓↓ AAccttiivviittaaţţiiii NNrrff22 ↓↓ EExxpprreessiiee ggeennee eennzziimmee aannttiiooxxiiddaannttee AAlltteerraarreeaa AADDNN,, ccaarrcciinnooggeenneezzăă SShhiibbaattaa TT,, eett aall.. PPrroocc NNaattll AAccaadd SSccii UUSSAA 22000088;; 110055::1133556688––1133557733.. ++ SSTTRREESS OOXXIIDDAATTIIVV
- 52. RRoolluull ssttrreessuulluuii ooxxiiddaattiivv ddiinn BBPPOOCC iinn ccaarrcciinnooggeenneezzaa SSTTRREESS OOXXIIDDAATTIIVV ↑↑ AAccttiivviittaaţţiiii NNFF--KKBB ↑↑ EExxpprreessiiee ggeennee pprroo--iinnffllaammaattoorriiii ↑↑ IINNFFLLAAMMAATTIIEE GGrreetteenn FFRR.. CCaanncceerr LLeetttt 22000044;; 220066:: 119933––119999.. ↑↑ PPrroolliiffeerraarreeaa cceelluullaarraa ↓↓ MMooaarrtteeaa cceelluullaarraa pprreepprrooggrraammaattaa ↓↓ AAppooppttoozzaa,, ↑↑CCrreeşştteerree şşii pprroolliiffeerraarree cceelluullaarrăă,, AAnnggiiooggeenneezzăă,, MMeettaassttaazzaarree IINNIIŢŢIIEERREE ŞŞII PPRROOMMOOVVAARREE CCAARRCCIINNOOGGEENNEEZZĂĂ
- 53. CCoonncclluuzziiii BBPPOOCC rreepprreezziinnttăă oo ccoommppoonneennttăă aa uunnuuii ssiisstteemm ccoommpplleexx ddee ccoommoorrbbiiddiittăăţţii,, aa ccăărroorr iinntteerrrreellaaţţiiee eessttee ddeetteerrmmiinnaattăă ddee ssttiilluull ddee vviiaaţţăă,, ffaaccttoorriiii ddee mmeeddiiuu,, îîmmbbăăttrrâânniirree şşii ssuubbssttrraattuull ggeenneettiicc.. VViiiittoorruull mmaannaaggeemmeennttuulluuii BBPPOOCC ttrreebbuuiiee ssăă aadduuccăă oo mmaaii bbuunnăă ccaarraacctteerriizzaarree ffeennoottiippiiccăă şşii oo aabboorrddaarree iinntteeggrraattăă aa aacceesstteeii ppaattoollooggiiii ccoommpplleexxee,, bbaazzaattăă ppee pprriinncciippiiiillee mmeeddiicciinneeii hhoolliissttiiccee..
Notas del editor
- USA National Hospital Discharge Survey analysed more than 47 million hospital discharges for COPD (8.5% of all hospitalisations) that occurred in the USA from 1979 to 2001 in adults .25 yrs of age. Estimated prevalence of hospital discharges with selected comorbidities in patients with and without COPD, NHDS 1979 to 2001. Bars represent the age-adjusted percentage with SE bars. Black bars show patients with COPD (either as primary or secondary discharge diagnosis). White bars show patients without any mention of a COPD discharge diagnosis. IHD ischemic heart disease; CHF congestive heart failure; RF respiratory failure; PVD pulmonary vascular disease; TM thoracic malignancy. The prevalence of all listed comorbidities is different across COPD categories (p 0.01). Holguin F, Folch E, Redd SC, Mannino DM. Comorbidity and mortality in COPD-related hospitalizations in the United States, 1979 to 2001. Chest 2005;128(4):2005-11.
- USA National Hospital Discharge Survey analysed more than 47 million hospital discharges for COPD (8.5% of all hospitalisations) that occurred in the USA from 1979 to 2001 in adults .25 yrs of age. The prevalence and in-hospital mortality of many conditions were greater in hospital discharges with any mention of COPD versus those that did not mention COPD. Of interest, a hospital diagnosis of COPD was associated with a higher rate of age-adjusted, in-hospital mortality for pneumonia, hypertension, heart failure, ventilatory failure and thoracic malignancies (fig. 3). In contrast, a hospital diagnosis of COPD was not associated with a greater prevalence of hospitalisation or in-hospital mortality for acute and chronic renal failure, HIV, gastrointestinal haemorrhage and cerebrovascular disease Holguin F, Folch E, Redd SC, Mannino DM. Comorbidity and mortality in COPD-related hospitalizations in the United States, 1979 to 2001. Chest 2005;128(4):2005-11.
- Impactul comorbiditatilor asupra prognosticului BPOC – mortalitatea dupa internari pentru exacerbarile BPOC
- Componenţii chimici ai fumului de ţigară, sau diferiti poluanţi iritanţi cu rol dovedit in etiologia BPOC, activeaza celule de la nivelul mucoasei bronsice, celulele epiteliale sau macrofage. Acestea elibereaza factori chemotactici (chemochine) prin care sunt recrutate alte celule inflamatorii circulante. O parte dintre aceste celule elibereaza proteaze care determina distrugerea fibrelor de elastina, cu distrugerea peretilor alveolari si apariţia emfizemului. La aparitia emfizemului contribuie si limfocitele T citotoxice care actionează sinergic, putand induce apoptoza pneumocitelor de tip I (prin producere de perforine, granzyme, etc). Proteazele au ca efect şi stimularea secretiei de mucus la nivelul glandelor bronşice cu hipersecretie de mucus. Macrofagele si celulele epiteliale elibereaza factori fibrogenici, o importanta parte a fiziopatologiei BPOC fiind determinata de fibroza cailor aeriene mici.
- As part of the chronic inflammatory process, tumour necrosis factor (TNF)-a receptor polymorphisms are associated with increased severity of disease, possibly due to enhanced TNF-a effects. Also, C-reactive protein (CRP) levels can be increased directly by TNF-a and other cytokines. Elevated CRP and fibrinogen may be crucial in the pathogenesis of cardiovascular disease. Reactive oxygen species released as a result of COPD may enhance the likelihood of a patient developing cardiovascular disease, diabetes and osteoporosis. IL: interleukin; ?: unknown; +ve: positive. Fabbri LM, Luppi F, Beghé B, Rabe KF. Complex chronic comorbidities of COPD. Eur Respir J 2008;31(1):204-12.
- Increased arterial stiffness has important hemodynamic consequences. The increased velocity of the reflected pressure wave augments aortic pressure in late systole, causing an increase in pulse pressure, due to increased systolic BP and decreased diastolic BP. As a consequence, myocardial oxygen demand and left ventricular afterload are increased, whereas coronary perfusion is reduced, leading to subendocardial ischemia (13). Furthermore, increased left ventricular afterload promotes left ventricular hypertrophy, a recognized independent cardiovascular risk factor (38). In the vasculature, increased pulse pressure alters the cyclical dynamics of the arterial wall connective tissues, promoting vascular remodeling, an increase in arterial wall thickness, and plaque formation (39). Thus, arterial stiffness may be both a marker for and a cause of cardiovascular disease. PAs, consumul miocardic de oxigen, postsarcina ventriculară, scad perfuzia coronara, ischemie subendocardica, modificari perete arterial pro ATS
- Legătura dintre afectarea funcţiei respiratorii în BPOC şi modificarea rigidităţii peretelui arterial ar putea fi generată de inflamaţia sistemică din BPOC
- Both endothelium-dependent and endotheliumindependent vasodilation is significantly impaired in patients with stable COPD. Airflow obstruction and systemic inflammation may increase the risk of cardiovascular disease in patients with COPD.
- Afectarea funcţiei rspiratorii prin disfuncţie obstructivă în BPOC se corelează cu creşterea riscului pentru HTA, independent de acţiunea altor factori de risc (varsta, sex, fumat, indice de masa corporala)
- Gariani K, Delabays A, Perneger TV, Agoritsas T. Use of brain natriuretic peptide to detect previously unknown left ventricular dysfunction in patients with acute exacerbation of chronic obstructive pulmonary disease. Swiss Med Wkly 2011;141:w13298. doi: 10.4414/smw.2011.13298.
- Medina AM, Marteles MS, Sáiz EB, Martínez SS, Laiglesia FR, Rodríguez JA, Pérez-Calvo JI. Prognostic utility of NT-proBNP in acute exacerbations of chronic pulmonary diseases. Eur J Intern Med 2011;22(2):167-71.
- In 2010, Barr et al, showed that the extent of emphysema and airflow obstruction are linearly related to impaired left ventricular filling, reduced stroke volume and lower cardiac output without changes in the ejection fraction. The study included 2816 patients with COPD. Left ventricle end-diastolic volume, stroke volume and cardiac output were measured by magnetic resonance. The extent of emphysema (expressed as percent emphysema) was defined as the percentage of voxels below −910 Hounsfield units in the lung windows on computed tomographic scans. The airflow obstruction was measured by spirometry. A 10-point increase in percent emphysema was linearly related to reductions in left ventricular end-diastolic volume (−4.1 ml; 95% confidence interval [CI], −3.3 to −4.9; P&lt;0.001), stroke volume (−2.7 ml; 95% CI, −2.2 to −3.3; P&lt;0.001) and cardiac output (−0.19 liters per minute; 95% CI, −0.14 to −0.23; P&lt;0.001).
- Wagner PD. Possible mechanisms underlying the development of cachexia in COPD. Eur Respir J 2008;31(3):492-501.
- Landbo C, Prescott E, Lange P, et al. Prognostic value of nutritional status in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999;160(6):1856-61.
- Wagner PD. Possible mechanisms underlying the development of cachexia in COPD. Eur Respir J 2008;31(3):492-501.
- Itoh T, Nagaya N, Yoshikawa M, et al. Elevated plasma ghrelin level in underweight patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2004; 170: 879–882
- Afectarea funcţiei rspiratorii prin disfuncţie obstructivă în BPOC se corelează cu creşterea riscului pentru DZ, independent de acţiunea altor factori de risc (varsta, sex, fumat, indice de masa corporala)
- Study was undertaken to evaluate the presence of the metabolic syndrome in COPD patients who participated in a cardiopulmonary rehabilitation program.
- The metabolic syndrome was frequent in overweight/obese patients with COPD. Obesity in COPD was associated with a spectrum of metabolic and inflammatory abnormalities. In the presence of overweight/obesity, patients with COPD would exhibit a metabolic and inflammatory profile associated with a higher risk of cardiovascular diseases.
- Man WD, Kemp P, Moxham J, Polkey MI. Skeletal muscle dysfunction in COPD: clinical and laboratory observations. Clin Sci 2009;117(7):251-64.
- Hypoxia - activity of enzymes involved in the Krebs cycle, fatty acid oxidation and the respiratory chain are reduced, whereas the activity of glycolytic enzymes is enhanced. Hypoxia may contribute to muscle wasting in COPD by a variety of mechanisms, including reduced anabolic hormone levels [61], increased levels of pro-inflammatory cytokines [62] and by the generation of ROS (reactive oxygen species) that contribute to oxidative stress Hypercapnia leads to intracellular acidosis that has marked effects upon muscle cell metabolism, including decreases in ATP, PCr and adenosine nucleotides Corticosteroids – steroid myopathy Nutritional Depletion Anabolic/catabolic hormonal inbalance - Reduced levels of anabolic hormones, such as testosterone and IGF-1 (insulin-like growth factor-1), Systemic inflammation - Elevated IL-6 levels are associated with radiological evidence of quadriceps wasting in COPD; TNF-α (tumour necrosis factor-α) levels are elevated in patients who fail to gain weight during a rehabilitation Oxidative stress - Free radicals (such as the superoxide anion and NO), when inadequately scavenged by antioxidants, can cause oxidative damage to lipids and proteins, significantly altering the activity of the mitochondrial respiratory chain complex. Increased levels of oxidative stress have been particularly observed during acute exacerbations [95] and during exercise [96], but also documented in stable COPDpatients [93].Treatment withN-acetylcysteine, an antioxidant, has been shown to reduce exercise-induced oxidative stress and improve quadriceps endurance
- Quadriceps maximal voluntary contraction force QMVC provides more powerful prognostic information on COPD than that provided by age, body mass index and forced expiratory volume in 1 s. Transplant-free survival for patients with normal and reduced quadriceps strength, as defined by a quadriceps maximal voluntary contraction force .120% or ,120% of body mass index. The curves are significantly different, p = 0.017. Swallow EB, Reyes D, Hopkinson NS et al. Quadriceps strength predicts mortality in patients with moderate to severe chronic obstructivepulmonary disease. Thorax 2007;62(2):115-20.
- Chest. 2011 Aug;140(2):331-42. Epub 2011 Jan 27. Physical activity is the strongest predictor of all-cause mortality in patients with COPD: a prospective cohort study. Waschki B, Kirsten A, Holz O, Müller KC, Meyer T, Watz H, Magnussen H. Source Pulmonary Research Institute at Hospital Grosshansdorf, Center for Pneumology and Thoracic Surgery, Grosshansdorf, Germany. Abstract BACKGROUND: Systemic effects of COPD are incompletely reflected by established prognostic assessments. We determined the prognostic value of objectively measured physical activity in comparison with established predictors of mortality and evaluated the prognostic value of noninvasive assessments of cardiovascular status, biomarkers of systemic inflammation, and adipokines. METHODS: In a prospective cohort study of 170 outpatients with stable COPD (mean FEV(1), 56% predicted), we assessed lung function by spirometry and body plethysmography; physical activity level (PAL) by a multisensory armband; exercise capacity by 6-min walk distance test; cardiovascular status by echocardiography, vascular Doppler sonography (ankle-brachial index [ABI]), and N-terminal pro-B-type natriuretic peptide level; nutritional and muscular status by BMI and fat-free mass index; biomarkers by levels of high-sensitivity C-reactive protein, IL-6, fibrinogen, adiponectin, and leptin; and health status, dyspnea, and depressive symptoms by questionnaire. Established prognostic indices were calculated. The median follow-up was 48 months (range, 10-53 months). RESULTS: All-cause mortality was 15.4%. After adjustments, each 0.14 increase in PAL was associated with a lower risk of death (hazard ratio [HR], 0.46; 95% CI, 0.33-0.64; P &lt; .001). Compared with established predictors, PAL showed the best discriminative properties for 4-year survival (C statistic, 0.81) and was associated with the highest relative risk of death per standardized decrease. Novel predictors of mortality were adiponectin level (HR, 1.34; 95% CI, 1.06-1.71; P = .017), leptin level (HR, 0.81; 95% CI, 0.65-0.99; P = .042), right ventricular function (Tei-index) (HR, 1.26; 95% CI, 1.04-1.54; P = .020), and ABI &lt; 1.00 (HR, 3.87; 95% CI, 1.44-10.40; P = .007). A stepwise Cox regression revealed that the best model of independent predictors was PAL, adiponectin level, and ABI. The composite of these factors further improved the discriminative properties (C statistic, 0.85). CONCLUSIONS: We found that objectively measured physical activity is the strongest predictor of all-cause mortality in patients with COPD. In addition, adiponectin level and vascular status provide independent prognostic information in our cohort. Leptin is a 16 kDa protein hormone that plays a key role in regulating energy intake and energy expenditure, including appetite and metabolism. Adiponectin is a protein hormone that modulates a number of metabolic processes, including glucose regulation and fatty acidcatabolism.[3] Adiponectin is exclusively secreted from adipose tissue (and also from the placenta in pregnancy[4]) into thebloodstream and is very abundant in plasma relative to many hormones. Tei-index – index combinat de performanta miocardica sistolica si diastolica
- Exercise training does not improve lung function, but it does ease other manifestations of COPD, increasing exercise tolerance, reducing dyspnea, and improving quality of life. Improved skeletal-muscle function is related, in part, to a reversal of deconditioning. Exercise training improves aerobic function of the muscles of ambulation. Dyspnea is mitigated by the reduction in dynamic hyperinflation that occurs when exercise- induced increases in the rate and depth of breathing result in inadequate time for full expiration, given the high expiratory airflow resistance. End-expiratory lung volume rises, and exercise is terminated when end- inspiratory lung volume approaches levels at which the high elastic work of breathing causes severe dyspnea. Exercise training reduces the ventilatory requirement and respiratory rate during heavy exercise, prolonging the time allowed for expiration and reducing dynamic hyperinflation. Desensitization to dyspnea occurs centrally as a result of exercise training; the underlying mechanism is uncertain. Decreased anxiety and depression are thought to result from increased exercise capacity and consequent increases in activities of daily living, coupled with feelings of mastery. N Engl J Med 2009;360(13):1329-35. Pulmonary rehabilitation for management of chronic obstructive pulmonary disease. Casaburi R, ZuWallack R.
- BMD – BONE MINERAL DENSITY Biskobing DM. COPD and osteoporosis. Chest 2002; 121: 609–620. Iqbal F, Michaelson J, Thaler L, et al. Declining bone mass in men with chronic pulmonary disease: contribution of glucocorticoid treatment, body mass index, and gonadal function. Chest 1999; 116:1616–1624 Incalzi RA, Caradonna P, Ranieri P, et al. Correlates of osteoporosis in chronic obstructive pulmonary disease. Respir Med 2000; 94:1079–1084
- Ionescu AA, Schoon E. Osteoporosis in chronic obstructive pulmonary disease. Eur Respir J Suppl 2003;46:64-75. Shane E, Silverberg SJ, Donovan D, et al. Osteoporosis in lung transplantation candidates with end-stage pulmonary disease. Am J Med 1996; 101:262–269
- Janssens W, Bouillon R, Claes B, et al. Vitamin D deficiency is highly prevalent in COPD and correlates with variants in the vitamin D-binding gene. Thorax 2010;65(3):215-20.
- Al-shair K, Dockry R, Mallia-Milanes B, et al. Depression and its relationship with poor exercise capacity, BODE index and muscle wasting inCOPD. Respir Med. 2009;103(10):1572-9.
- The main finding of this study is that patients who had a relapse after emergency treatment of obstructive pulmonary disease are more likely to report signs of anxiety and/or depression (Hospital Anxiety and Depression (HAD) scale). The patients received emergency treatment and were followed up for 4 weeks. The psychological status was assessed using the hospital anxiety and depression (HAD) scale questionnaire at the end of the follow-up period. Among patients who relapsed within 1 month (n 14), the HAD total score was 12.4 5.9 compared with 8.6 5.1 (mean SD) among the patients without a relapse (p &lt; 0.05). After making adjustments for age, gender, atopic status, treatment, and pack-years, the significant association between treatment failure and anxiety and/or depression still remained. Dahlén I, Janson C. Anxiety and depression are related to the outcome of emergency treatment in patients withobstructive pulmonary disease. Chest 2002;122(5):1633-7. .
- Incidence density of lung cancer is high in COPD outpatients and occurs more frequently in older patients with milder airflow obstruction (GOLD stages I and II) and lower BMI. A DLCO&lt;80% is associated with cancer diagnosis. Squamous cell carcinoma is the most frequent histological type (44%). de Torres JP, et al. Lung Cancer in patients with COPD: Incidence and predicting factors. Am J Respir Crit Care Med 2011;184(8):913-9.
- O metaanaliză publicata in 2011 a avut ca obiectiv evaluarea diferitor afectiuni pulmonare din punct de vedere al riscului de cancer pulmonar, determinat in mod independent de fiecare dintre acestea. Rezultatele arată un risc relativ de 2.04 (95% CI: 1.72, 2.41) asociat emfizemului pulmonar, 1.52 (95%CI: 1.25, 1.84) asociat bronsitei cronice şi respectiv 2.22 (95% CI: 1.66, 2.97) asociat BPOC.
- Conform rezultatelor mai multor studii, inflamatia şi stresul oxidativ par sa fie elementele de legatura in cadrul interrelatiei patogenice complexe dintre BPOC si cancerul pulmonar. Fumatul este cea mai importanta sursa demonstrata de generare a stresului oxidativ si a reactiei inflamatorii pulmonare in BPOC. Stresul oxidativ determina activarea a multiple mecanisme patogenice, factori de transcriptie, kinaze, factori epigenetici, care moduleaza raspunsul inflamator, ciclul celular si proliferarea celulara iar in cazul existentei unui background genetic si epigenetic care determina susceptibilitate, apar BPOC respectiv cancerul pulmonar.
- Expunerea la fumul de ţigară induce stresul oxidativ atat în mod direct, prin aportul de compuşi oxidanţi cît şi prin dereglarea unor mecanisme antioxidante endogene. Stresul oxidativ amplifica raspunsul inflamator si deregleaza activitatea mai multor factori nucleari de transcriptie, determinand disfunctii ale mai multor antioxidanti si enzime cu rol in detoxifierea celulara, la nivelul pulmonului bolnavilor cu BPOC, crescand susceptibilitatea acestora la cancerul pulmonar. [104, 200] Unul dintre acesti factori este Nrf2, in BPOC observandu-se o scadere semnificativa a activitatii acestui factor de transcriptie urmata de scaderea expresiei genelor pentru anumite enzime cu rol antioxidant la nivel celular, cu efecte in promovarea mecanismelor patogenice ale BPOC si cancerului pulmonar, inclusiv prin alterarea structurii AND [98] .
- NF-KB este un alt factor nuclear de transcriptie, a carui functie este dereglata de stresul oxidativ in BPOC. NF-KB este activat excesiv de stresul oxidativ determinând mai departe transactivarea genelor răspunzătoare de promovarea inflamaţiei. Studiile au evidenţiat activarea aberantă a NF-KB şi a genelor inflamaţiei la nivelul epiteliului mucoasei bronşice şi celulelor inflamatorii atât în BPOC cât şi în carcinomul pulmonar scuamocelular. [176–179] . In plus au demonstrat că NF-KB are atât un rol de promotor tumoral prin stimularea proliferării celulare şi inhibarea morţii celulare preprogramate cât şi un rol de iniţiere a carcinogenezei. [180] . In BPOC, NF-KB activeaza macrofagele la nivelul mucoasei bronsice acestea eliberand compusi oxidanti care determina alterarea structurii ADN la nivelul celulelor epiteliului bronsic. In plus, NF-KB determina amplificarea expresiei citokinelor proinflamatorii care au si efecte de promovare a angiogenezei tumorale, accelerare a cresterii celulare si metastazarii. Studiale au aratat ca expunerea prelungita la fumul de tigara a animalelor de laborator determina cancer pulmonar in urma activarii aberante a NF-KB si a raspunsului inflamator exagerat la nivelul cailor aeriene. [181]