KPATKA XAPAKTEPHCTHKA HA IIPOYKTA1. HME HA JIEKAPCTBEHHA IPOAYKT ViSIIbsTHIITENHA ATEHLMA M10 SIEKAPS pana Yaparepuemana Wa npogynra NwNOReHIe Crmpan Peer 2,5 wnsporpana pasaop sa mera | 5 nn AOLLORER, Spiriva Respimat 2.5 microgram inhalation solution | ite P.M man \pampauone WOM... LEO... 2. KAMECTBEH H KOJIMYECTBEH CbCTAB / 23M mB 0 Ne Ornensnoro KonnuectBo akTHBHO BeulecTBO € 2,5 muKporpama THOTponHyM 3a BrpbeKsaute (2 DBIPBCKBAHHA CBCTABAT E”IHA sMeKApCTBEHA 03a) H ¢ eKBHBACHTHO Ha 3,124 MuxKporpaMa THOTPOTYM Gpomaix Monoxnapar (tiotrapium bromide monohydrate). Tlosara, xosTo ce ocsoSoxasa, € 103a7a, KOATO ce AOCTABA 3a naLWneHTa criex NpeMHaBae Te MynonyKa. Tlomompy nemecrna c H3nectHo gclicreue: Tosa neKapeTBo ceutepaKa 0,001] mg GerrsankonMes xnopHA Ha BIPBeKRAH. 3a MaHMA CHHCEK Ha NoMOMHHTe BeMIeCTBA BYDKTE TO™KA 6.1. 3. JIEKAPCTBEHA ®OPMA. Pasrpop 3a wHxanans. Bucrsp, Gesunerent pasreop 3a Mixaziauia, 4. KJIMHHWYHH ABBE 4.1 Tepanesrwann noxasamus XOBB CCrupusa Pecrumar npeacrannasa 6poHxosiuaTaTop 34 NoJUIEprKAlllO TeNeHHE 3a OGeKYABAHE Ha cuMMToMTe pH nauuKeHTH c xpoHHUHa OGcTpyKTHBHa GeoApobHa Gonect (KOBB). Acta Crmpnna Pecnmmar e noxasant kato AOMbuIHHTeTHO NOLTSpAAMLO JeYeHHE ¢ OpOHXORMAATATOP MPH NaUWeHTH Ha BB3pacT 6 TONHIH HIM OBEHE ¢ TAKA ACTMA, KOHTO Ga HMA/IH EHO HIM TOBeYE TeaKKH ‘oGoctpaHHa npes npestxomnara romwta (Bk, ToUKH 4.2 5.1). 42 Josuponxa u na npuacxenne Hoaupooxa: JlekapeTneHnsr nporyKr € camo 3a HHXasaTOpHA ynorpeGa. TIanHHTeRAT Mowe Ja Ce HoCTABR H HSTIONSBA ‘eMHCTBEHO B HEXarIaTOP PecriMMar (Bx. TOHKA 4.2). Eqna nexapernesia 03a BKINOWBA ARe BNPKCKRAHNA OT MHXasIATOpa. TIpenopBHMTTEMMATa NO3a 3a BRSPACTHH C 5 Muiporpama THOTpOMMYM, OCROSOeHH OT sIKe BIPECKBAHHA OT HEXATaTOpA PecHuMAT, eH IST AHeBHO, no EHO M ChILO BPEME Ha eH. Tipenopswanara josa ne TpaGsa 1a ce mpesmurasa. Tipu sievesmero a acraa, mara nionsa ce OTHHTA Cites HAKO:IKO 103M OT JleKapCTBEHHA MPO} [BBApACTHH NAIMEHTH ¢ TEAKA ACTMa THOTPONMYM TPAGEA 2a ce HSHOMSBA KATO AOMBAHCHHE MixaslaTopHM KopTukocTeponan (= 800 ig Gyaes0HNA/AHeBHO WAH ekBHBALTEHTHO Cpe; eH KoNTposMpamt AeKApeTBEH MPOAYKT.TlanweHrH » Hanpennana ssspact Morat 2a wanos3BaT THOTPONHYM GpoMua, cncaBalikn npenopoyanara osuponka. TlauneirrH ¢ Gs6peunn yapexctaniia MoraT 1a HonOMSRAT THOTPONHYM GpoMNA, caemBaliKH npenopsanara ‘osuponka. 3a NauHeHTH CBE Cpeatia 10 TerkKa GLOpeua HeAOCTATSIHOCT (KpeATHHHHOB KAMLHC < SO m/min, sioxre TowKH 4.4 15.2). Tanners, crpaaaun ot YepnompoGua HenocTaTB4HocT Morar sia HstIo13BaT THOTPonHYM 6poMin, cnempaiixn npenoppuaitara xosmponKa (Box. TONKA 5.2). Tleduampusna nonyaayuer Acmua Tipenopsswreanara 2038 mpH nanyeHTH Ha BEpacT OT 6 20 17 romMHH e 5 MiKporpaMa THOTpoNHyM, COcpoGoeHH OT sIRe BIPLCKBAHHA OT HHKXasIATOpA PECTIHMAT, AHH ITLT AHEBHO, 110 EHO H CEItIO BPeMe Ha ena. Tipu tonoumn (12 20 17 roms) ¢ Teskka acrua, tHorponHyM TpaGBa Aa ce HsHOMIBa KATO JOMBIHEHHE KEM ‘Tepamusra c MuXaNATOpHH KopTHkocTepoH.AH (> 800 - 1 600 jig GyaesoHNL/ANeBHO MIM eKBHEATeHTHO CepexcTno) H enMit KoHTpomMpall eKapeTBeH NPOAYKT, HAM KATO AOMBAINEHHE KEM TepamHsTa c irxanaTopHH KopTuKocTepontH (400 - 800 jig GyAesOHHL/HEBHO WAH eKBUBALIEHTHO CPenCTBO) H Ba KoHTpoaMpauui :lekapeTBeHH npoAykTa. Tipu zeua (6 a0 11 romwH) ¢ TexKa acTMa, THOTPOTIHYM TpaGBA Na Ce HSNOM3BA KATO LOMBAHEHHE KEM ‘Teparwsra ¢ HiXaaTOpHH KopTHKoCTepoHaH (> 400 Hg GynesoHHLY/AHeBHO WM eKBHBANIEHTHO cpencTBO) ‘eANH KOHTpOmHpaM eKapCTREH MPORYKT, WK KATO AOMTRTHEHHE KEM TepaTINATa ¢ MHXAETOPH Koprukoctepown (200 - 400 jig Gyzes0RNA/aHeBHO WIM eKBHBAeHTHO cpexeTBO) H £ABA KONTPOAMpaLNt sleKapeTbenit npozyKra. Bee ome ne ca yeranonens GesonacHoctra w eikacHocTra Ha Crimpipa PecriuMar mpi eua Ha BE3pact oT 6 0 17 roaHHH c ymepeHo Texka acTMa. Bce oute He ca yeTaHoRenH Gesonachoerra H edpHKacHocTTa Ha Crmpupa Pecnmmar npi eta nog 6-ronmuma stspacr. Hanwuinte 2aHnH ca onHcaHi B TONKH 5.1 45.2, Ho IMpentopekH 3a JosMpoBKaTa He NOraT 1a GbAAT AATeHH. XOBB Tiuncea cborseria ynorpeGa Ha Cnpusa Pecruwar mpi eua H oHOUNH nog, 18-ronMULHA BBSpacr. Kucroaya gu6po2a Expuxacnocrra # Gesonacnocrra #a Crmpiea PecnuMar He ca yeranopen (Bx. TouKn 4.4 15.1) ‘Hasina npastoxenne ‘Toa slekapeTBen mpoaykr e caNo 3a HHXaaTOpHO MpHLAOaKeHMe. TTksIHHTENST Moxke fla Ce NOCTABH Hsmiom73Ba caMo B HHKXallaTop 3a MHOTOKpaTHa ynoTpeGa Pecriuwar. Pecnumar e unxastaropHo yerpolicrso, koero reHepupa cnpelt 3a MHxaraua. TIpeasiizer € 3a ynorpeGa or eaHH NauMeHT H e npeaHasHaveH 3a MHOTOKPaTHH 103M, AOCTABAHM OT EHH TTHHTEN. Vinxanatopet 3a MHoroxparsia ynorpe6a Pecnwar nosBoasa CMSHA Ha ITBIHMTeAA, KATO MOE sa Ce warionsBa ¢ 0 6 masmuuTena. Tlaunenrure Tps6pa ja npowerar ykasaHHsra 3a TOBA KAK sla HSMO-I3BAT HEXasATOpA 34 MHHOTOKpATHA -ynorpeGa Pecmuar, npenit a sanowHar 2a wsnoxssar Cnupusa Pecnunar. 3a aa ce ocurypH npaMio npHarave Ha slekapcTBeHHS MposYKT, Ha nauMeHTa TpsGwa Ja Gwe NoKAAHO ‘OT eka WIM APYT MecMIVACKM CEMMAIHCT KaK ja HSTONSBA HHIXaIATOpA. ‘kasans 3a uw a WixarraTopa 3a MH morpe6a Pecnuwat Zleuara tpa6ea na wsnosrsnar Crmpina PecmMar ¢ nowourra Ha BBspacTeH.Heo6xoamMo e, naueHrst Ja Hsrio73Ba TO3H HHxanaTop CAMO BEJIHBK JIHEBHO. Ipu sexo usnosiseane ce npunaret JIBE BIIPbCKBAHHA. Mennwren © Axo Crmpipa Pecnmmar He © wanom3sax nosese oT 7 niH, TpABBa fa Ce MPbCHe BeAIEK KEM genera. ‘© Axo Crmpipa Pecmmmar ne ¢ wsnos3sax nosese or 21 s1HH, TpaGBa na ce noBTopar cTEMKH 4 210 6 or ,Jlogroronka 2a ynorpe6a", 10 nospara Ha aeposouna seorsa, Cae TOBA Ja ce NOBTOpsT erunkut 4 20 6 ome TpH ETH. Kax nannenrsr 1a ce rpwxn 3a mmaxanatopa 3a MHoroxpatna ynorpeba Pecaumat MyHalykor ce nounicrna, akmOMMTesIHO MeTAsIHATA HACT B HETO, ¢ HARIOKHEH MEK THAT WIM CAMO ¢ KBPIa, owe Beak cenMHMHO. ‘Cra6o oGeauneranane Ha Haxpaiinnka 3a ycra He ce OTpasasa Ha paGorara c MHKaATOpa 3a MHOTOKpATHA -ynotpe6a Pecnmmar. ‘Axo e HeoGxosINMO, HXALIATOPBT 3a MHOrOKpaTHa ynorpeGa PecrmMaT ce NOMHCTBA OT BBHIMHATA 4aCT C HapnarkHeHt Mex TLIaT. Kora aa ce ewe wxaaaropa Axo naumerrsr e wsnoss8ax MEXaTaTOp ¢ 6 maaTHHTe;R, TpAGBA a B3eMe HOBA onaKoBKa CnupHBa Pecrmmar, chxepokautia Hixanarop.Tloaroronxa 3a ynorpeGa 1. Orerpanspanie ua mpospasnara ocnona © Kanauxara rpa6sa aa e sarsopena. ¢ Harvicnere oGesonacasauina ‘eneMenT H eaHoBpeMentto c ‘Tosa, msatspnaitre npospasnara ‘ochoBa ¢ Apyrara PKA. 2. Mocranane wa meanurens © Tlocrasere maamutens 8 Muxazaropa. ‘* Tlocrasete wixanatopa BEpxy ‘TaEpaa MOBEPXHOCT M MpHTHCHETE ‘sapawo, jloKaTo ce uye mIpaxeaHe. 3. Caeaene na mbanutenute 1 mocraname wa npospaynara ocnona © OrGenemere 8 noserara wepxy cevixera Ha wirxanaropa 6pos Ha monmrreaute, © Tlocrasere npospasnara octiona ‘o6parHo Ha MacToTo ii, H naTucueTe, 2oKaTo mpakHe. 4 Sanpprane © Kanavxara tpaGna aa ¢ sarsopena. © Sameprere npospaynara ocHoBa no ocoKa Ha CTpesIKHTe BEPXY eTuKera, XoKaTO ce Hye mipaKBaHe (noaoBHH o6opor).‘5. Orpapane © Kanasxara tps6ea aa ce orsopit Hamano. 6. HarncKane Hacowere mirxanaropa Kos 3eMaTa © Harneuete GyTona 32 ocpoGoxapane Ha 203aTa, © Sarpopere kanaukara. Tlostopere cremn 4-6 20 nomsa na aeposomma weraa. © Carex nompara ma aeposoana pra, nostopete cromkH 4-6 ome ‘pa mem. Cera muxaaroptr e rotos 3a ynorpeGa m me nocTanut 60 sanpsexsanus (30 2031).Exeanepua ynorpe6a 3ABBPTAHE ‘© Kanaskara rpaGpa 2a e sarpopena. ‘* 3ABBPTETE npospaynara octosa no ‘ocoka Ha erpenkirTe BUPXY eTHKeTa, OKaTO ce uye upaxeave (noz0BHH Gopor). OTBAPAHE © OTBOPETE amano kanaykara . HATHCKAHE © Hsanmaitre Gastio 1 xv16oKo. ‘ Tlocranere yeranre cH nutstHo oKo70 -MyHAmtyKa, Ges a saxpusate OTBOpHTE sa pusnyx. Hacovere mirxanatopa KoM repaoro cH. * Hoxato sanusare Gasto H x4160K0 pes yerara, HATHCHETE 6yrona 3a ‘ocpoGoxasale Ha jo3aTa H npombnkere aa Bavupare Gast, ‘TONKOBA TBAFO, AOKONKOTO € BESMOxKHO. ‘© 3eaptaxre smuianero 3a 10 cexynant HAM JOKaTO MoxeTe, ‘* Tlopropere crnku ,3ABBPTAHE*, »OTBAPAHE* ,HATHCKAHE, 4a npwenene Ha mannara 1034, ocurypena oF 2 snpecKsanina. © Barsopere kanauKara ia witxanaTopa 10 caeapautata my ynorpeGa. ro Aree Poors Pri)Kora aa ce samenu mbanureaa na Cnupupa Pecnumat Vinankaroper 3a nositre noxkassa Ko.IKO BnpECKBAHMA OCTABAT B ITbTHHTeNA. ® Ocrapar 60 anpscksanns & Ocranar no-wanko or 10 snpscxsanua. HeoGxoaumo e, a ce B3eme Hop matHHTe:. a Thamurreasr e caxpuina. 3assprere npospaunara ocHoBa, 3a na ce pasxna6n manuTens. Cera mixanaropsr € B sakmouena nosmiHs. Hasaere maniesa oT wHxaciaTopa. Tlocrasere HOB Mrmitres, 2okaro Toi mpakve (Hanpasere cnpaska ckc cTsnka 2). HonMsT matHiTes ue © Maiko nlo-snyaeH B CpanHenne c mspsus (npombinKeTe oT crenka 3). He sapanaiire 1a ocrasHre OGparHo npospayHata OCHOBA, 3a fa OTKIONHTTE MHXasIaTOpA, 4.3. Mpormsonoxasam CoppxuyscranremHoct KEM THOTPOTHYM GPOMHLL HHIH KDM HAKOe OT MOMOUIHHTE BeWLeCTBA, HI6POeHH B ‘Touka 6.1, HIM KbM ATPOTHH HIM HETOBHTe MPOHSBONIM, HaMpHMeP HIpaTpONIHyM WH OKCHTPONHYM. 44° Cnennasnm mpeaynpexaenus m npeanasun Mepku mpm ynorpe6a Tomomn semeersa Bensaawonnesiirr xiopia woake 2a npHMIH Xpiiose H 3aTpysNeno mane, [anesTiTe c acTMA ANAT ‘RosMueH prick 3a TesM HexTenaHH peaKKI. ‘Tuorponnym Gpomna, mpercTaniapa GpouXosMTaTATOp 3a NOLIBPAKALLO NeYeHHE, 3a NPHAOXKEHHE BENWTEA AeBHO, NOpazH Tash NPHIHHA He TpAGBA Ja Ce H3NIONIBA 3a HAYAIHO eYeHHe Ha OCTbP NPHCTSN Ha GpoHxocna3bM HH 3a O6seKYaBAaHe Ha OCTpH CHMMTOMH. B cay4aii Ha OcTbp MpHeTeN TpaGea sa ce woniox3ea Gepso aelicrBauy Gera-2 aronucr. ‘Crmpusa Pecrmar we TpaGea za ce warionaea kaTo MoHoTepanis 34 acTwa, TlaumesTuTe ¢ actwa TpAGEa Ja (GhnaT ChpeTRAHH ja MpomBKABAT NpHeMa Ha poTHBOBEsMaNMTesIHA Teparus, T.e. UNXANATOPHHL KOpTHKOCTepOHIH, MpHeMaHtH Ge3 MpoMaHA Cale BHBEXKAAHETO Ha CnupHiBa PecnuMan, OPH KOrATO cHMITTOMHTe HM ce NOROGPST. Buamoxuia € nossara Ha peak Ha cBpEXYyBCTBHTeAHOCT OT Gups THN cHes MpHAOKeHHE Ha THOTPONMYM pom pasrop 3a wixanauis. Tlopaau weropara anrruxommnepruaiia akTHBHOCT, THOTponMyM 6poMHA TpxGea ja ce nputara c OcoGeHO [BHVIMaHMe MPH MAUMeHTH Cée 3AKPHTOBTAINA FayKOMA, XHMIEPILIASHS Ha MpOCTATHATA A:e3a HLTH OOCTPYKUMA Ha MIMFiKaTA Ha TIMKONHNS Mexyp. Jlexapcraennte nponykrH 3a MHXAaNaTOpHO MPHOKEHHE MOTAT Ja NPEAMSBHKAT MHXATATOPHO-MHAYUMPAH Gpoxxocnasem. ‘Tuorponnyy rpaGna 1a ce Wsnom3Ba ¢ NOBHIUICHO BHMMAHHE MpH NauWeHTH c TPeKAPAH HACKOPO My unibapxr penn no-Maiiko OT 6 Mecetia, HecTaGHLTHa HIM KHBOTOSACTpaMaBaLla CopACHHA Ap! CcopAesia apwTMns, Havtaraila HHTepECHLMS, HTK NPOMAHA Ha JeHeHHETO C AeKAPCTBA Mes ni ronmna, xocmmranHsaua 3a cbpaesia HenocraTEAHocT (Kae II] wan IV no NYHA) npes mToawna, Taxnea MauHeHTH ca GHTH HBKCOYeNH OT KAMHHTIHHTE MPOYSBAHHA, & TESH CRCTORKHA Morar 2a Ghat nOBNHsIH OT AKTHXOMMHEpTHSHHA MEXANIESEM Ha eHicTBHe. Teil kavo nasmenre KoHteHTpallin ce yRenkwapaT mpH HaNanena GnOpeuna GYHKUMA pH NauMeNTH cue pesto 20 Texxo 6x6pesnio yapexnane (kpeaTHAHKOB KMMpBHC < 50 mV/min), TAOTPOMHTYM Gpouia Moke 1a ce npnnara, camo ako ONaKsaviaTa Nonaa Hananlvaea noTeHUMaHs pHcK. Hama awnrocpoynH 2aHHH 38 pinoxkeHHeTo Ha npomyKTa TPH NIaUHeHTH ¢ TexKO OD6peNHO YeperAHe (BK. TONKA 5.2). Tlaunermare tpaGea na Seaat npemynpercn 2a BHNMaBaT cHpsAT Ja He nonamie B OwTe. TpaGpa 2a Gbuat MpeaynpexeHid Comlo TaKa, Ne TOBA MORE Mla NOBENE NO BOULABAHE HaIH OGOCTPAHE Ha 3aKPHTORTAHA Taykoma, 601Ka HAH AUCKONG}OPT OT CTpalta Ha OWHTe, BpeMeHHO 3AMEIAABAHE HA SPeHHETO, UBETHA KPBrope HAH TleTHa, CBDPIAHH Coc SAYEpBABAHE Ha O*FTe MOpAsiM KOMIONKTHBANHA KOHTECTHA H KOpHEATCH ook, Taunenture rpa6sa Hesa6aano 2a npexparat ynoTpeGara Ha THOTpONHYM OpoMH H 2a NOTEpesT ‘CBBET OT CHeWMAANCT, aKO Ce NPORBH KAKBATO H 1a € KOMGMMALIA OT TE3H OHH CHMITOMH, Tlo ppente na anrixonmneprsnara Tepams ce Ha6monaBa cyxOTa B ycTaTa, KOTO NpH NpombmDKHTeNEH NepHon Moxe a € acouMmpata Ec 3b6HH KapHecH. ‘Tnorponnym 6pomug He Tpx6sa fa ce npyara noseye oT BeaMEK sHeBHO (Bx. TONKA 4.9). ‘Crupipa Pecumar ue ce npenopsuna mpi KicTosHa (bH6posa. Axo ce Hsrlom3Ba NPH nauKeHTH ¢ KUCTOIHa ‘buGposa, Cnmpwna Pecnwat Moxke 2a NOBHLIM MpHsHayHre H CHMsTTTOMHTTe Ha KHCTOSHaTA ¢puGposa (aN. ‘CepHOsiiN HEAeTaHH peaKUMH, GenompoSuH OGOCTpAHHA, HH EKUMH Ha AMKATENTHATE METHULA). 45 Boaumoselicroue c apyru sexaperbeum mponykrw # pyri (popmi Ha BsaHMonelicrEHe Bonpekn, ve He ca nponeskiann KaKKTTIHH HaTuNTBaIHA 3a BsaHMOReFiCTBHA, THOTPONHYM GpoMiAA € pHnaras enHlonpeMenHo ¢ ApyrH nexapeTBenH MpoayeTH, Ges fa HMA KIMHHMH AOKasaTeTCTBA 38 SlekapeTpenn ssanMorelicTBHa. B Ta3H rpynia BAWAT CHMMATHKOMHMETHUIH SpoHXOAMNaTaTOpH, MOTIEIKcaHTHN, CTepOrAH 34 TepopastHo H HHKAsIATOPHO MPHIOKEHHe, aHTHXHCTAMHHH, MYKOMMTHL, TeBKOTPHEHOBM MORMDHKATOPH, KpOMOHH, axrrH IgE Tepannsa, WecTo MplinaraHH MpH neyeHeTo Ha XOBB acraa. He e ycranonenia npomaria Ha excmooMuMaTa Ha THOTPONMyM npH YnoTpeGa Ha ABaronelicTBaMH Gera 2~ aromnera (IJIBA) HH wHxanaTopHH KopruKocrepoman (KC), He ce npenops4pa eniospementioro MpwioxceHHe Ha THOTPOTIHYM OpoMM c APyTH AHTHXONAHEprHUHH AeKapeTSCHH CpeZCTBA, Toit KATO 10 TOSH MOMEHT eKapcTBeHOTO BIAHMOeHICTBE HE @ MPOY'EKO. 46 — @epruanter, Opemennocr u kupene Bpemennocr Vina wHoro orpannuena nan 3a ynorpeGara wa THOTponHyM pH Gpemennn enn. Mpoysnanisra mpH 2KHBOTHM He TOKAGBAT NPEKH WIM KOCBEHH HEraTHBHH exheKTH TO OTHOUIEHHE Ha PenpoxYKTHBHA ‘TOKCHMHOCT MIpi 03H OT KIMHHHHO 2HavenHe (ex. TONKA 5,3). KaTo mpeanasia MapKa ce NpenlopEyEa ynorpeGara Ha Campisa Pecnusar a ce w36area no apeme Ha GpemeHnocr. Kepwene He e wapectio aa THoTponys 6poMiey ce exckpeTHpa B MaHHHOTO MilxKO NH xopa. BuMIpeKH IpoRedeHHTe KIMAMSHH APOYBAHHS MPH TpHGAYH, KOHTO MOKASEAT, He MAIKO KOAMYECTEO THOTPOFIMYM Gpowng ce ekexpeTupa B KBpMaTa, ynorpebara Ha Cnupusa PecnuMat He ce npenoppssa B repHona Ha kcepMente. THoTponuy 6pomiut e Bemectso ¢ npomwoKHTemHO AelicTBHe. Koraro ce EHMa pe pomipkaBanie/npexparapaie Ha KBpMeHeTo HIM lpossokasaHte/npeKpaTaBaHe Ha eHeHHK Pecrumar, TpaGba s1a ce B3eMe Non. BHIMAHHE OWaKBAHATA 3a ETETO M0134 OT KEPMEHETO fst Malikara rioasa oT xevenutero cbc Crmpwsa Pecnwsar.Sepranuter Hana nanan eoMHTAKH aH 3a THOTpOTHTyM. TipeaKusHHO Npoy"BaHe, MpoBEeHO ¢ THoTpoMAY He © NOKaAANO HHKAKEH HOKCANM PeAKIINH Mo OTHOMENHE Ha GepmanuTera (BK. TO:KA 5.3). 4.7 Edexra pupxy cnocoSuocrra 3a mopmpane # paGora c Maman He ca nposexkaiaHn mpoy'ania OTHOCHO edbeKTiTe BBPXY cTIOCOGHOCTTA sa to‘HPaHe H paGoTA c MALIKI. Tlospara na samasHiocT, saerieHo sioKaaHe WIE TaBOGOTHE Moke a OKBKE BIIAAHHE BLPXY ‘cnocoSHocrTa 3a wopkpane 4 paGora ¢ Maun. 4.8 Hexenaum aexapersens peaxuunt 1a Mt Muoro of 16poeutite HexellaHH sIeKapcTBeHH peaKiun MoraT 1a ce EHDPKAT ¢ ANTHXOMMHEPTHMHHTE cpolicrsa Ha THOTponHyM 6pomn. S me Ba6 HCH BI Yectorara, onpeneneta 3a HexenaHHTe slexapcrseHH peaKLH, HB6poeHH NO-noTY ce Gasupa Ha Heobpa6oreHH CTerteHH Ha NPOsBICHHE Ha HEmeTAHH eKapCTBEHH peaktIMH (Tc, PEAKMAH, KOHTO Ce nputincnar a THorponaym Gpomil), HaGmonaBaHM ® rpymara, seKyBaua c THOTPORHYM B 7 riauue6o- KOHTpOnHpaHn KaHRUsE MpoysBatna np XOBB (3 282 naunesrru) w 12 rxaueGo-Kowrpomparn JcTHHHMHTH poyssanii pH BESPACTHH H NeaaTpHeNT TrauMeHTH ¢ actMa (1 930 nauMeHTH) ¢ HepHoA Ha JleMeHMe, BapHpAMl OT HETHPH CEMMHIL 20 enKa TOME. YectoTanre Kateropun ca onpeslenenn no caeaNaTa KOHBCHUMR: senozo vecmu (21/10); xeemu (21/100,<1/10); nevecrmu (21/1000,<1/100); peoxu (21/10000,< 1/1000); sanozo pedwu (<1/10 000); c weussecmna 4ecmoma (om nanusnume danHu He mooice Oa Ode Hanpasena owenxa). ‘Cucremo-oprania kaacuxanua curaaeno MedDRA | Yectora Wecrora XOBB Actua | Hapymenyst na meraGomeawa yw xpavenero Tlexwaparauuts Crempectia ‘Crenssecria wecrora secrora Hapyeina na wepanara cuctena Samaawocr Hewecta Hevecra TnasoGonve Hesecra Hevectu Bescpane ‘Peak Hevectu Hapywenia wa ownre Taaykoma Peaka CiHenspectua wecrora Tlonuieio serpeosHo nansranie Peaxn C nenssecra ectora Banrarneno BMKTIANE Penk C wemseecTHa wecrora (Copaeuin Hapywenns Tipenepawo srianene Peaxa Taanirraun Penna laakamepna Taxnapana Penn 10sectora Taxnnapans Penkn Crewspecria secrora | PecnupaTopum, IpbaHH M MenMacrHMaTHH wapyIeHHR Kauumna Heyecti Heyectu @apunret Hevecrn HevectH oun Hevectu Hesectn_ Enmctaxcuc Peak Penkn Bponxocnasea Peaxn Heveor Tlapmnror Penxn C newsneeTHa wectora ‘Cunysur C rewsnectua CHenssecrHa sectora secrora | CroMauio-ipesay HapyINesHa Cyxora e yerara ect ‘Hevecr Koncranaui HevectH Penk# | Opodapmrireaina kanmanosa Hesect Heweert Auegaris Penxu C nemspecriia secrora Tactpoesodareanen pepayxe Peakn C HenspectHa sectora ‘3w6eH Kapnec Peaka ‘C Henspectua wectora Busnavenhe Ha BeHunre Penka Peaxn Tnoceur Penka ‘C mewseectua ectora (Cromarar C Hewseectna Penk ectora Vinrrectunanna oScrpyxuma, axmowrrenko napamrrusen | C wewssectiia ‘Crewspectia eye wecTora wectora Tanene C HeuspectHa C HewspectHa sectora ecrora Hapywer 4 ara AH, na etema O6pus Hevecra Hesecra [Tipypurye. ‘Hevecrn Peaxn. "AHIHOHERpOTHMeH E71eM Peakn Penk Ypruxapus Penxn Peanut ‘Kowa unbexyua, KoxHa 9388 Penkit ‘Cnenspectua secrora Cya Kona Peaxw Cremspectia ecrora (CapExyypcTsuTeanoct (BKMOUHTeAHO peaKuMu oT Gsps | C HeuapecTHa Peak mn) yectora Anabaiacrasna peaxunn C newspectaa Cnenseectia nectora sectora H: Jeni /EKYMHO-CRE/I ‘cvenmmrennara Texan Tloayeane Ha crane C nemspcctHacn HnKowrre nen ‘Sanpxxa na ypana Hexeom Cnewsnectia ectora Tsypua Hexeera C newssectua sectora Vicbexuns Ha ypaHapHna TpaKT Penxn Peakn Onncanne na Ht HY NeKay HM B Korponmpan kamit4nn npoyseans npx XOBB ecto naGmonapaire HexesaHM peaxiyin ca ANTUNOAMMePIHSHH HexXenaNH exapCTHEM PeAKIIMM, TAKHBA KATO CYXOTA B YCTATa, KOHTO BLOHHKBAT MPH MpHGaWwrenio 2,9% or naunesrire, [Ip acta YecToTara Ha peakuistTa cyxoTa B yerara e 0,83%. B7 xaMHHuHH npoyusanns np XOBB cyxorara B ycraTa BoaH s10 npexbcpane Ha s1eeHHeTO NpH 3 OT 3.282 nauutesrru, nexyaann c THorpormnye (0,1%). TIpexnceadte Ha Je4eHHETO TlOpamH CYxOTa B YcTATA He € cpoSuieno 8 12 KaMHUEH npoyBaHHs npH acrwa (1 930 nannenrH).. Cepnoanit Herxenantn peaklIMl, CBEPSAHH C AHTHXONMMEPTHHHH e*PEKTH BKIOMBAT KAKTO ay KoMa, KOHCTINAIUA H MiTeCTHHATHA OBCTPYKIU, BKMOWHTE,IHO NApAnHTHYeH HNEYC, TAKA CBUIO H SARpEARKA Ha pana Deanarpasna nonysauns Aanure 3a Gesonackoct Bkmo4uRaT 560 neqHaTpAsHN NauMeHTH (296 nauHeHTH Ha BEspact oT ] a0 11 TogMHH 4 264 naueHTH Ha BESpact oT 12 10 17 roaMHH) oT 5 naueGo-KOHTpOTHpaHH KTMHHSHH Mpoy'saHia c nepHoan Ha newenne Mery 12 ceammun 0 1 roawHa. YecTorata, Tana TexKecTTa Ha HeXe.AHHTe PeakUMAH TPH NesMATpHYEETA MONy.NaUAA Ca CXOIM C TESH MPH BSPACTHH NaUWeHTH uebysHM nonyazauM ‘Bramoxktia e Monviliena Moana Ha aTHXOAMHEprHMNH HEAeTANM PeaKUAH MPH NaUWeITH B HANpeAHATA pspact. (CroSuapane Ha nomosHpan HexeaHH peakinHH ‘CroSumapanero Ha noaosHpann Heenan peakunn oxen paspeulaparte 3a yoTpeGa ta eKapeTBeHHA poster € saxo. Tosa nosnoaasa sa npOATBMKH HaBMOAeHHeTO Ha eOTHOWIeHKeTO NOA3A/PHCK 3a aleKapeTseHia mposykt. OT MenHIVICKHTe CneUMAAHCTH ce HSHCKBA 1a CLOOUIABaT BeAKa NOROaHpaHa Hokenavia peaxupis pea Mamasirrensata areHuns Mo Jlekapersara, yn. ,Jlatan Ppyes” Ne 8, 1303 Cospns, ‘Ten.; 35928903417, ye6caifr: www bda bg. 49° Tipeaosupane BHcOKH 2031 TAOTPOMHYM SpONHA MOFAT 2a NpesGBMKAT AHTHXOTMHEDTHYEM NPHSHALM H CHMITTON. Bunperu Tosa, He ca HaGsHOnaBAHH CHCTeMHM alfTHXOAMHEprHMHH Heenan EGeKTH TH SAABH oGponos, ee pHAOAeHE Ha emHOKpATHA A038 OT 340 MuKPorpaMa THOTPOMHYM GpOMA. B nombruenve, He ca Ha6monaBaHn 3Ha4HMM HEKEIAHH JeKApCTBEHM PeaKLMH, OCBEH MPECHXBAHE HA yerara/reproro 4 sMraBHuaTa Ha HOCHATa KYXHHa, cnem 14 .HEBHO MpHAOKeHHE Ha 103 10 40 Muxporpama THorponiyyM 6pomi, pasTROp 38 MEXANALMS, MPH 3ApABH AOOPOBOALD, C HSKINOYEHHE Ha BHO Nawananaile Ha nprrTOKa Ha CIIOHKA OT 7-MHL EH HATATHK. 5. @APMAKOJIOTHUHH CBOHCTBA 5.1 Oapmaxoausamusua cxolicra ‘@apmaxorepanestmuna rpyna: JIpyrH AekapeTBcHH cpeacTaa 3a OOCTPyKTHBHH 3aG01aBAHHA UW ANAATeAIHHTE BTHULA, HEXATANTH, axtTixonmHeprHust ATC Koa: RO3B BO4 2Haunn wa geficrane Tuorpormys Gpomna npescransssa npoxBsoxHrentio-nelicTBaMt, cheLupHYeH arsTarOHACT Ha MyckaphHositre petterrropH. TIpHtexana cKoxeH apMHiTeT KBM NOZTHNOBeTe MYCKAPHHOBH petterrropH M; 0 Ms B anxareminre msTauta, THOTPONMyM GpOMELL KOHKYpeHTHO H OGparHMo arrTaronsHpa Ma- PenerrTopeTe B raakata MYCKY.atypa Ha OpoHXire, Karo aHTTaroHM3Hpa XOAMHEprHHAR (GporroxonerpreTHBnna) edbeKr na aneTHAXoAMHa, KoeTO BOAH HO peaKcaMiA Ha SpomxnaTHaTa Myckyaatypa, Edberror Geute tososasHicHM H pomiuxwTenoctra My € nosewe or 24 aca. Kato N- NeTBEPTITYEH AHTHXOAHHEprHeH ATeiTr, THOTPOTIBYM POM € AOKamTHO (6pOHXo-) cenlexTHBeH e1eR HuIXaNaTOPHO MpHAOXKeHHe, KATO NeMONCTpHPA NPHEMAHBH TepanienTHUNH FPAHAAH, NpeAR NPosBATA HA CHeTeMETH arTHXomMHepriinH expeKTH. Dapmaxoawnamnunn edextn ‘Tlwcounaumsra 4a THoTponyM Spout, ocoGeHo oT Ms-peuerrropwre € moro asta, noKasBalikn ‘SHANIFTEAHO NO-;MsTbT MOTYDKHROT Ha ANCOUMALAN OT HAGMOAABAHHR MPH HNpaTponHyM. JIcouMALMaTA OT Ms-penterrropie e no-Gxpsa oTKoakoTO oT Ms, KoeTO NpH yRKUHOKAMI in vitro Mpoy'MBaHHR, pasKpH (jamterieano KorponHpana) peuerrtopHa cyGTunka ceneKmusHocT ua Ms npesesxoxaaua TasH Ha Mp, Bucoxara espexrusHocr # witoro GapiaTa peulerrTopHa AMCOUMALH H OKaMHA WHKNGHTOPHA ceneKTHBHOCT ‘KAHMHHHO Ce NpORBABAT B SHAYHTTeAMa H sTeATOTpaliva Gpouxomvaarawus NpH rauneHTH ¢ XOBB H acta, Kimura eduxactiocr 1 62301 5B TIporpamara 9a kanniunio paspaGorBarie asa III skmo4sa ae I-roaMun, aBe 12-ceaMHaHH H ABE 4 CceaMICIH, panaOMHaHpait, ABofHO-cxlenH npoyusanns npH 2 901 naumesTH XOBB (1 038 npHenaunt osu oF 5 jig TuITponHyss). EAHOTOAHIDHATA NpOrpama ce CECTOH OT ABE fLIatleGo-KOHTPOAMpaHH poyusasus . [pete 12-ceammunn npoy¥sanns ca axTuanio (unparporuys) - 1 1iae60-KOHTPOAMpAHH. Bewukite wect npoyusaHis BKIOMBAT HsMepBaHHA Ha GeronpoSuara dyHkuna. B oranenne, aBere 1- TORHUIKH Npoy'8aHHA BKIMONBAT SApABHHTE MapaMeTpH KATO AMCHeR, 3ApaBHOOBYCAOBEHOTO KANECTBO Ha 2xnboT M edbeKTH BEPXY OGocrpaHUsTA, . HH KIMHINUEH NpoyuEAHTS Bexodpobua dyuxyua Tipiicrkermeto Ha THOTPonHyM pasTBop 3 HIXATAIHS BEAM ANEBHO, HoH 10 SHAUHTEAHO MOAOGpEHE Ha GenoapoSuara dyskuns ((bopcupan excnmpatopen oGeM 3a | cexysna, DEO: 4 popcrpan swraten xanawiTet, @BK) 30 muyyrs clea MpAAOXeHeTO Ha mpeara 1032, 6 cpasHenne ¢ ruaueGo (PEO, cpenno noao6petiHe Ha 30 munya: 0,113 murpa; 95% noneprrenes nHTepsan (J1M):0,102 a0 0,125 sutrpa, p<0,0001). FlonoSpernero Ha GenonpoSwara (iyHKUNA ce nlomTEpxa 24 aca npH CTaGHLAHO HHBO B ‘cpansienne c iaue6o (DEO) cpeano nono6perne: 0,122 mmtpa; 95% IIH: 0,106 a0 0,138 surrpa, p<0,0001), ‘DapmakonHHaMiIHo CTAGHAHO HHBO ce MOCTHTA 3a e,tHa CeAMANA. (Crupusa Pecnumar skauremHo noxoSpasa BEJ\ (Bypxos excnpatopen xeGur ) cyrpeuinus H BevepHiLA, wamepen criopen aHeBHHTe 2anvicH Ha naUMeHTa, B cpasHeHHe c niiaweGo (BEI cpeno nonoGpenne: cpenno nono6penne Ha cytpunta 22 Limin; 95% JJM: 18 n0 55 L/min, p<0.0001; newep 26 L/min; 95% JIM: 23 10 30 L/min, p<0,0001). YnorpeGara va Cnupisa PecnaMar soaH s10 HawanasaHe ynorpeGaTa Ha oGnexsasaiuo Cepronelicreauu Spoxxoawrararopu w cpanvenme c runaueGo (cpeaHo noMIDKeAME Ha -ynorpeSara wm c 0,66 caysas aneBHio, 95% JIM: 0,51 0 0,81 exyuas sHeBHo, p<0,0001). Bposxonniatapauusr edpext Ha Crmpusa Pecnamar € novIepkaH mpes UeAKa ENHOTOAMILEH MepHOM. Ha npwioxenne, Ges npusHaun Ha npHBHKBaHE, Jucnues, kavecrao Ha 24EOT, cBEpIAHO Cée 3apaneTo, OG0C; XOBB. HH eANOTOAMUIHH “mpoywsanna Awenves CCrnpuna Pecruvar aHaunrenno nosoGpasa cocTosHHeTo Ha sincrites (oueHeHo no Transitic Index), 6 cpasHenne c ruraue6o (cpenxo nonoGpenne 1,05 exmmmun; 95% JH: 0,73 20 1,38 p<0,0001). Tlonobpennero ce noaepaa npes ueNKA NepHon Ha TeHertHe. 8Kavectno Ha 2xiH07, CREp3AHO Che SpaBeTo TlonoGpennero Ha cpeqHus peay.rTar MpH OleHKA Ha KAMECTBOTO Ha ANBOT Ha riauMesTITe (HsMepeHO nocpencrsom St. George's Respiratory Questionnaire) np Cnuspna Pecnumar 8 cpapnenme c ruratte6o 8 pas tia anere I-roaMumHi npoywpanns e 3,5 enmnnun (95% JIM: 2,1 10 4,9, p<0,0001). Yerapn ctenento TowIDKeHHE Ce NPHEMA 34 KTTHMHNHO SHAHHMO. OGoerpstie Ha XOBB B 7px eavioro MIN, paHAOMMSHpAKH, ABOMHO-crenH, niaule60-KoHTpOAHpanH KCTHHAYAH NpOyNBaHHA niewenvero cbc Crmprpa PecniMar Boni 20 3HaYHTeNHO NAMANABAHE Ha pHCKa OT OGocrpane Ha XOBB 8 cpasnene c ruraute60. O6octpanero Ha XOBB ce nedurnpa karo ,Kownitexe oT HOKE Be pecriupaTopHH cuGurTus/cHumTroMH c MpORWTAHTeTHOCT OT 3 ANH WIM NOKeYE, KOETO Haltara NPOMAHA B TeveHHETO (npeannceane na anTHOMOTHUn WHLIK CHCTEMEM KOPTHKOCTEpOHAH H/T CBIEECTBCHA NPOMAHA B HasiavieHoTo pecrimparopHo sleveHe)”. JlevexneTo cc Cnmpusa PecrTHMaT BOZH 20 HOHKACH PACK OT XOCTINTaTHIANMs B CnencTaHe Ha OGocrpane Ha XOBB (sHa4MMO B MOAXOTAMIO CTATHCTHYECKH 3AxpaHEHOTO mmpoKooGxsaTHo mpoyupaie 3a oGocTpaHHA). OGobmernar anaes OT ane asa III npoy-eains H OTHENEH aHeZTHS Ha AOMBTEMTeAKO Mpoy4BaHe 3a oGocrpsnis e noxasaHt 8 TaGauua 1. Bewski pecrinparopii eKapcTBa c HSKIMOYEHMe Ha aHTHXOMNeprHUH v Gera-aronNcTH c NPOMDTKHTeNHO JeficTeNe ca GHIA NOSBONEHH KATO CBITBTCTBAILO sAeHENKe, HANpHMED Gupso neticraauun 6era-arouNcrH, KOPTHKOCTEpOMAAK 3a MHXamlaTOpHa ynOTpEGA, KeaHTHH. BeTa—aroHMCTH Cc npombsrxwresno aeHicrane ca 61H NOSBOACHN KATO CBITSTCTBAUIK B MpOy'BAHeTO 3a OGOCTpAHE. TaGmua 1: Craructiseckn aan na oGocrpamasra Ha caMmromuTe Ha XOBB 1 xocriraausupann XOBB ‘oGoorpanis npx ralinesTu ¢ ymepeHo Texka 0 MHoro TexkKa XOBB. Tipoyseane | Kpaiina uen ‘Cumpusa | ThraueGo | % nawanasatie | p-eTolinioct (Nery, Pecimmar a pucKa Nesane6o (95% JM) * T-ronmumn | JIM 0 mepso XOBB | 160° 86 2 0.0001" basal GocrpsHe (16 0 409° mpoyysanna, —[ Cpeawa vecrora Ha 0.78 100 | 2 0.002" oGutananws’ | exommxnane Ha (8.2033 oGoctpanusra K6M (670,653) mannenTo-ronwKa Bpene 0 mpsa 23 020° XocnHTanHsania 3a (16.20 51)* XOBB oGocxpave ‘Cpenna wectora Ha 0.09" oir 20 0.096" xocmrrasinupaiit (-4.20 38) OG octpaHHs KEM naunenro-romuna Troamuno | fim no mepeo XOBB | 169° iT 31 <0.0001° basa IG oGoetpane (23.40379 npoyasane sa | Cpeana yecrora ta 0.6 08? 21 <0.0007" oGoctpania | susHHKBaHe Ha (13 2028) oGocrpannsra xeM (1939, 1953) | nauetrro-ronuia Bpeme s10 mppa 2 0.003 xocriTamHsauH 3a (10.20 418 XOBB oGocrpanie Cpeana vectora na 0.12" 0.15" 9 0.004" XocTHTATHSHpanit (710 30" Gocrpars KeM nawwewro-roania "'Bpeste ao mopno cHGnTHE: ANH C neeTINE, 0 KONTO 25 % OF NALUENTINTE HMaT HONE exo XOBB oGocrpane /x0e XOBB oGoctpaue, B umumaane A 25% om nsauebo nayuenmume wvam oBocmpane a den 112, doxamo na Cr “25 % nam oboempae na dew 173 (p=0,08): 6 npoyrasane B25 % om naawyeBo nayuenmume uam oGocmpane na dex 74, dosamo ua Cnupusa Peemuam 25% rw4am o6oompane wa den 149 (p< 0.0001), Crenesra na puck (hazard rato) ce ouexsasa oT Cox nponopuyonaies woes sa cremienra me puicka TIpoueMrer Ha nasa.tee 1a pci ¢ 100 (Ishazar ratio). * Poisson perpecis. Hawancianero a pwcea e 100 (I-crenen wa cxorwouennte). * Oban anus e npexnapireavo onpesenen, KoruTO e ceauasaH ANAMHTLT Ha npoy’ssansa. Kpalure Hes 3a oG0eTpAME ca anasrIMo nonoGpenM pH CAMOETORTENKIFTE BMAIUOM HA ABETE EANOTOAMIINM HSMMTAOHHA. IrocpowHo at HO NpoyuBaHe Ha THK Tiponeaeno ¢ arocposHo, panoMHsHpano, ABojiH0-CHsMO, AKTHBHO-KOHTpONMPAHO KIKHHIHO NpoyABAHe Cc nepnoa Ha npocnenspane 10 3 ronHHH 3a cpaBHeHne Ha edyHkacHocTra H GesonacHocrTa Ha Capua Pecnumar 1 Crupapa HandiHaler (5 711 nautterrrn ca npremant Crapitea Pecmimar, 5 694 nausentH ca prema Crupitea HandiHaler). Frepaassie xpaiitm ue-rh ca 61H Bpemero AO MbpBOTO OGocrpAHE Ha XOBB, apemeto 20 cmmpr nopaan BeHIKH pin H B nomHSTuNTBaHE (906 natMeHTH) Hali-MHcbK DEO: (npean npanarane Ha 038). Bpemero 20 mpsoro oBocTpatie Ha XOBB € wncneno non06no np npoyssaneto cbc Crupisa Peenumar ¥ Crmpiea HandiHaler (koedmumen 1a puck (Crmpusa Pecrinat/Chupusa HandiHaler) 0,98 ¢ 95% J1H or 0,93 x0 1,03). Cpenmusr 6poit zr s10 mpsoro o6ocrpane Ha XOBB e 756 aunt 3a Crupupa Pecnaamar u 719 ani 3a Cnupusa HandiHaler. Bporxonanararopsusr eext Ha Crupusa Peommar nposmnkasa maz 120 ceaMMun H ¢ cXoaeH C TOM Ta Chujpuea HandiHaler. Cpeanara paxnixa mpi cpasrenme na DEO; na Crmpnpa Pecnmmat cnpawo Cruprna HandiHlaler ¢ Ginna -0,010 1 (95% IH -0,038 20 0,018 1). B npoyusanero p nepnoaa cnen myckaHe Ha nasapa TIOSPIR, cpasiapauio Cruipusa Peonmmar v Coupusa HandiHlaler, cmroproctra ropaa eeaka npirsinta (BKMOSHTENHO MPOCTEAABAME Ha AMSHEMHA CTATYC) © Gni7a cxoana c Koe*baunerT Ha puck (Cnupitsa Pecninwar/Cruprsa HandiHaler) = 0,96, 95% JH 0,84 - 1,09). Cnormerernamara excnosnuna na newenne e Gua 13 135 w 13 050 nanento-roaMAH. B maayeSo-kosrponmpano Npoy'eave ¢ npOCMenseAHe HA KHBHCHMK CTATYC AO KpAR Ha WGpAHKA Nepuor, (Crmpusa PecrmMar noxasea sHauierenio HNCTeHO yaeTHYeHHe Ha CMEPT NO BCAKA NpHYHHA B cpaBeHHE C maue6o (cootHomerne Ha vecroTaTa (95% Jopepitrenen unTepsar) oT 1,33 (0,93, 1,92) excnosMUna Ha seven coc Cruipina Peenunat or 2 574 nauverto-ronsii, karo Ha6moaaBanoto HoBHUNeKME Ha ‘CMBpTHOCT € MpH MALIHeHTH c HaBeCTHM PHTEMBH HapywweHHa. Crutpusa HandiHaler e nokazana 13% TOHIDKeHHE Ha pricka OT eMBPT ((KOedHIMEHT Ha PHCK, BKAOYBAKI NPoceARBaHe Ha AKUBHENHS CTATYC (uorponuyt/nnante6o) = 0,87; 95% J1A, 0.76 10 0,99)). Excnosuunara Ha newenwe coe Campuna HandiHialer e Guna 10 927 naunenro-ronmun. He e waGatonasan noBmulien pHcK OT eMEPT NpH NoxTPyNaTa TAUIHeHTH ¢ HaBeCTHH PHTDMEH HAPyMIEHHR B rLIalleGo-KOHTPOMMpaHoTO KIHHHUHO TIpoy4BaHe CHC (Crmpusa HandiHaler, kaxto 4 np cpasnurrentoto npoywsae TIOSPIR wa Cripuea Pecnumar # Cripupa HandiHialer. ‘Kamnnusia eduxactocr 4 Gesomacocr npx acta Kannnswara nporpama or gaa III np nepcHcTapauta acTMa nH SLSpacTHH BKIMOWBA J18e EAHOTORMILINM, pangomienparn, wofino-crem, tayeGo-KOHTPOaHpAHH Mpoy4BaHAR MH O6uNo 907 nauKerTH c AcTMa (453, nonrysananos Crupiea Pecmumat), mpHemau KoMGuHauna or MKC (2800 pg Gynesonwa nHeBHO WH exbupaestHo cpexcre0) ¢ JYIBA. B npoy4eanusra kato MspsH4HK KpainH uenH ca BKMONeH HaMepsanuis Ha GenoapoGHaTa byaxnns H TEKH OGOCTpAHHA. wus PrimoTinA-asthma B apere [rox npoyssaninx npu cHMmTOMaTHHHH nawWieHTH, NpHeMALI NloaDpaaIO AeCHHE ¢ Haii= anko HKC (2800 jig Gynexong aweeHo HIM exruzanenTHo cpercteo) nue JUBA, Cnupnsa Pe oxaaea RAMHHUHO IMAM NOZOEpeHHA Ha GenoapouAra hyHKUAS B cpaBHEHHE C NTaLeGO, K: arion3na KATO JOMMAHEHHE KuM OcHOBHOTO sleveHHe. 8Ha 24-ra censmua cpentoro noaoSpenne Ha crotinocTire Ha maxon DEO; H DEO » kpaa Ha AO30BHA worreppan e cboreeTHo 0,110 mrrpa (95% JIH: 0.063 20 0,158 swrpa, p >0,0001) # 0,093 aunpa (95% ZH: 0,050 x0 0,137 aurrpa, p<0,0001). Iono6penveto wa Genoapo6nara dynxuna cpastenHe c ruiaue6o € TosspyaHo 6 pankere Ha 24 aca, B npoyspatisra PrimoTinA-asthma nevennero Ha cumrtomaruunire nannerrH (n=453) ¢ HKC noc ILJIBA nmoc mHorponmys: naMasiaea plicka OT Texku GocTpaitas Ha acrMara c 21% epaBlenie © sleNennero Ha cHMITTOMaTHMHH rauneHTH (n=454) ¢ KC nmtoe JIIBA nmoe naaxe6o. Hamanenuero na pitcka cpemto KaTo Gpoli TexKn OGOCTPAHHA Ha acTMaTa HA TlAUNeHT 3a romHHa e ¢ 20%, Tosa ¢ noukpeneno oT 31% NoHWKeHHe Ha PHCKA 34 BAOUIABAHe Ha ACTMATA H 24% NOHWKEHHe Ha PHCKa cpeavo Karo Gpoll Biouaeanus Ha acrwara Ha nauqenT 9a rosa (Bx, TAG 2). ‘TaGanua 2: OSocrpaHHa mph cHMMTTOMATHYHN nauMeHTH, npHemann HIKC (2800 Hg 6ynesoNNA pHEBKIO IH exBHBaneHTHo cpezeTBo) naoc JJIBA (npoyssani PrimoTinA-asthma) Tipoyssanna | Kpalinn wenn Compusa Tlnane6o, Karo. | % P Pecmmmar, zomsaienne — | nowioxenne | croiitoct Karo koM Hall-Mako | Wa pHcKa gomsanenne — | HKC#JUIBA | (95% JIM) Kou ati-manko | (N=454) HKCYIBA (N=453) cape T= Tibi a0 1-20 Texxxo | 282° 226" 21 0,0343 ronMuna oGocrpane Ha (0.38) npoyspanix | acrwara or asa II, open ‘Cpeaen 6poi Texxxn | 0,530 0,663 20° 0,0458 maka ‘oBocrpanna a 036) actwara Ha naunent a roanna ‘Twn a0 1-80 315" 18" ae <0,0001 omapane Ha 18,42) acrwara Cpeaes 6polt 2.145 2,835 2 00031 roulanainns Ha 0337) acraara Ha niaunent 3a ronMna, * S800 ne Oyaeson ARERHO HAH eXBHBENEHTHO CpEAETBO Cuoruomenieto na pucks, aopepHresusT nirepaan x p-erollocrTa ca nomytenu ypes Mose uit Koxe 3a NponlopiwonaswHTe uckone, mpi Koro exHcrReMAsT epexr ¢ nevenwtero, TIpoueTer a noxiexeHNe Ha paca e 100 (1 ~pHEKOBO CHOTHOUICHHC). " Bpene 10 mspa0 ex6iHe: 6pof nH € aewenue, 20 xoraro 25%/50% oT raumenTaTe ca noy~HaN Hal-maKo €aH0 GepHO3HO oGocrpate/ mnowasate Ha acara * Crotnouennero ret yecrovara ¢ tlonyseHo pes perpecuotien wosen a Tloacon, mpi KoTo norapirawunaa ekenosnipis (8 ‘onmn) ¢ mapawerspnr sa orwecraatte. MpoueNrworo Kowinxenne Ha piteka € 100 (I-NecrOrio CMoTHOMICHNE). eauorpiia nonyanuis: XOBB 6Enponelickara aretiuia no nexapersara ocaoGoxkaana OF 3aTbDKeHHETO 38 MpeOCTABANE Ha pesysTTaTHTe or mpoysannsra coc Cnupysa PecrnuMar 6b BCHSKM noarpynM Ha NeaHaTpMuMaTa NonynauMA NpH XOBB (wx. To-Ka 4.2 sa ungopMaun oTHOcHO NeaMaTpHUHA ynoTpeGa Actma Bewakn npoyssanvs 8 komiwasara nporpama or asa II] npx nepewcTHpauia acta ¢ neaHarprruH nayenry (or | 20 17 roan) ca 61H panmoMtsHpaxH, ABolHo-cnentt H mialeGo-KoWrTpOsHpaH, BousKH aunenTH ca Guin Ha OcHoBHO NeHeHHe, axMousamto HKC. Teakxa acmua FOnowu (om 12 do 17 zodunu) B 12-ceammstoto npoy4sane PensieTinA-asthma ca Grim BKmOveHH OOulo 392 mauwetTH (130 oT TAX Ha sneyexue cbc Cnuprpa Pecnumar), Ko#TO ca HM@IH CHMITOMH MpH MpHeM Ha BHCOKH 203K MKC c ean Kostpostpau rekapersen nponykT Hak cpemHa aosa MKC ¢ asa KOTPORMpaMN eKapeTReNK MpOAYKTA. Tipu naumerta Ha spspact or 12 20 17 roam aHcoKa os MKC ce onpesiena karo 03a oT > 800 ~ 1600 jig GynesoHnA/anesHo HAH exsHBareHTHO cpescTBO; cpeaa rosa HKC ce onpexena Karo 2038 oT 400 - 800 jig 6ynesonruy/AHeBHO HH eKBHBAAerTHO cpencTeo. JoMBnHNTeAHO, naubeHTH Ha Buspact oT 12 20 14 roan morar aa npemat HKC 0 03a > 400 ug OyaesoHna/aresHo WIK eKBHBATeHTHO cpeACTBO ¢ HOME ome ex KoHTposTHpaul JeKapeTBeH npoayKT HAH > 200 yg GyAesoHNA/AHeBHO WK eKBHRAICHTHO ‘cpeneTBo H TOK Ba KOHTTPONHpALLK jeKapCTBeHH NpoayKTa. B ropa npoyusaie npa npwiarane Ha Cruprea Pecrumar AOMRIHHTeTHO KEM OCHOBHOTO AeHEHHE ¢ naGmonaBavio nojoGpanaHe Ha GenoapoGHara by HKiues B cpasHenne ¢ nxatieGo, emnpeKH Ye pasnMKire B MiKoBiITe CTORHOCTH 4 cTOHHOCTHTe R Kpas Ha OI0RHA HATepRAT Ha DEO) He ca GaH cTaTHCTHMECKH, sHaMM. ‘+ Ha ceawmua 12, cpennoto nonoGpenne B nluKosiTe CroliHocTH H crORHOCTHTe & Kpaa Ha 10308 uurrepaaa na DEO) € 6u10 ceorserHo 0,090 nutpa (95% JIM: -0,019 20 0,198 msrrpa, p0,1039) 0,054 supa (95% J1H: -0,061 20 0,168 arpa, p=0,3605). ‘+ Ha ceammua 12, Crmpusa PecnaMar stausrrenio nono6psna cyTpeulrnre W BeNEpHATe CTOHOCTH Ha BEJ| (cytpemen 17,4 Vmin; 95% JIM: 5,1 10 29,6 Vin; nevepex 17,6 liin; 95% JUH: 5,9 10 29,6 Umin), lena (om 6 d0 11 zou) B 12-ceammanoro npoyseane VivaTinA-asthma ca 6iu1H axmovenn o6uto 400 naunenrH (130 oT TAX Ha severe coc Cpa PecrmiMar), KoHTO ca HMA CRMITTOMM TPH HpHeM Ha BHCOKH 03H HKC c enw oNrponmpau sekapeTaen MponyKT Mant cpeaa stosa HKC c ssa KORTPonMpaMil sleKapeTBeHA NPOAYKTA. Bucoxa sosa HKC ce onpezens karo 028 oT > 400 ug GynesoH/aHeBHO Hmm ekKBHBATEHTHO cpencTEO; cpestta noaa KC ce onpeneas kato aoa oF 200 - 400 pg GyaesoHA/aNesHO HAH exsHBaneHTHO cpeaCTEO. B Tona npoysisane Crupuea Pecnimar riokassa HavHTenHO nodOGpaBane Ha GenoapoGHaTa bYHKUMA B ‘cpanHienve ¢ ruiaueBo Koraro Ce npalara OMbsNHTENHO KBM OCHOBHOTO sIeHeHHE, ‘© Ha ceantnua 12 cpeaHoro nonoGpenve B nuiKonitTe cTofinocTH H crolitocTHTe B Kpax Ha 2OI0BHA wurepean Wa DEO: ¢ Gux0 chorserHo 0,139 murpa (95% JAM: 0,075 20 0,203 sump, p<0,0001) 0,087 swerpa (95% JIM: 0,019 0 0,154 auerpa, p=0,0117). Vutepena acmua Onow (om 12 60 17 eoounu) B eakoroanuoto npoyueare RubaTinA-asthma ca Gian sxmovernt oGuio 397 maunenry (134 of Tax Ha -aewenne coc Cnupisa Pecrmmar), KonTo ca uma CHMHTOMM mpH TpHeM Ha pens 2osH HC (200 - 800 ng 6ynesonna/aeRHO WmH exBHBaNeHTHO cpeacTRO NA NaueHTH Ha BEapact oT 12 20 14 roaMHH ~ 800 yg Gyes0Hna/aHeBHO Ha eKBHBBAIEHTHO CPeAETBO MPH NauMEHTH Ha BEspacT OT 15 20 17 Crmipnsa Pecniwar noxa3ea sHawnererHo nosoGpaBane Ha dywunsTa na Genta apo6 cnpano, Korato ce Npiiara JOMEAHHTe”HO KbM OCHOBHOTO -leveHHe. wFleya (om 6 do 11 200unu) B eqnoroammmoto npoy4pane CanoTinA-asthma ca Sunw sxuoYeHH O60 40] nauueHra (135, rroaysasanys Crtupipa Pecnuuar), Kouro ca HMANH CHMIFTOMH MpH cpedtHH 20H KC (200 - 400 ug Gyaesowty/AeRHO HAH exEHBaNeHTHO cpejteTRO), Ciixpitsa PecruMaT NoKasBa SHauuTenHO NoNOGpaBANE wa Genoapoduata yHKuna B cpasenHe c TuaueSo KoraTo ce MpHAarA NOMBIHHTETHO KEM OCHOBHOTO sewer. ‘Heoua (or 1 x0 5 rons) B 12-cenmuuno patuiomrs4pano, aBoHtHo-caano, niane6o-KoHrrpoaMpano npoywsane Ha dasa T/T (NinoTinA-asthma) e Guto npozeneHo mpu o6mo 101 aeua 31, nonyyasaun Cnupuea Pecrwatr) ¢ Acro a OcHOBHO sleveHtHe, KoeTO BkmIOWBa KC. OGemna Kamepa Aerochamber Plus Flow-Vu® c Macka 3a muue ¢ vonomeana pl npanerave Ha HSMMTRAHOTO AleKapcreoro npH 98 nawHeHTH. Tiepsinara wen #a npoyseareto e Gna GesonacHoctra, mpoyusaneTo Ha espuxacHoctra © 6w10 © wacrenosaTencKa Wea. Bpoar 1 npouentsr nawyierri, choSUMKIK HexeranH neKapcTBeHM peakunn (HJIP), HesaByciMo nan ca G17 ceDp2ani, ca noxkasaHn 8 TaGsmMua 3. Bpost Ha HexxeTaHHTe peakilMH, CHRpSAHH c acrMa, € GH NO- Hcbx mp Crupuea Pecniunar p cpasvenue ¢ niae6o. MIpoy4sarenuite OueHKH Ha e*pKaCHOCTTA He noxasear pasnuka npa Crrmpia Pecrumar cnpamo nuraiteGo. TaGnmua 3: Yectora wa naywerrrute c HUIP, choSumasany mpi noseve or > 5 nausetrrn 8 mpoywsasiero NinoTinA-asthma (newa Ha sespact of I a0 5 roa) Thaaue60,n (%6) ‘Crumpusa Pecan (6) [Bpof canner 34 (100.0) 31 (100,0) Hanonesra ¢ HTP 25 (73,5) 18(58,1) [Hasogapimrus 5(14.7) 265) [Mere na roprarre auxareann 12,9) 5(16,1) rama [Actwa® 1029.4) 265) [Tnpexcin 6(17.6) 3.7) * MedDRA repent no npeaTioniraina Tepwint CEMA" ¢ , BAOTTaRaHe wa AcTwaTa wm ,OoeTpste wa acTuara* Enponelickara archuuia 0 sleKapcTpata ornara 3ammiDKeHHeTO 3a NpemOcTaBANe HA PesysTTATHTe OT mpoyseanusra cbc Crupisa PecnMar npu nenWerpH4H nallMeHTH Ha BEapacr non 1 ronHHa (Bx. TOWKA 4.2 3a nribopwauia ornocHo yrorpe6a w nemMaTpHATa). WU \cHocr 1 Gero1 TIporpasara sa :AUHUYKO paspaGoTBaHe npH KuCTOSHa GuSpo3a BKMIOUBS 3 MHOTOLEHTPOBH NpoyBANMA nnpx 959 nauneTH Ha enspact 5 Meceua H noseve. MauxeHTH non § roaMuHa Bb3pacT ca HBnOSBAIM crrelicep (Genta kamepa) (AeroChamber Plus®) ¢ macka H ca BKIIO¥CHH caMO 34 OUCHKA Ha GesorlacHocTTs. Acre rmaotHu npoysisarns (nosoonpexenauio Dasa II npoyspane W noTespxaasamo ‘asa III npoyBare) cpanriapar ecpextitre na GestonpoStara dynxuna (npouert or npemsireHoTe DEO) AUC oan Hall-HucKa croiitiocr Ha DEO:) na CrnprrsaPecrtamar (tHotponyM 5 yg: 469 naunesm) cnpao nuiatte6o (315 anwerri) 8 12-ceammanit, parvioMIBHpaHH, ABoliHo-c7emH nepHomH; NpoysBaneTo Dasa Ill sKTOWBA cbinlo zesFOCpo4HO, OTKPHTO ymRunKeHHe 20 12 meccua, B Tes! NPoy4BaHits, BCHYKH pecMApaTopHH eKapeTaa, ¢ HaRUHOeHHE Ha AHTHXOMMHEprH4HUTe ca GHLAH paspeUeHH KATO MPHAPYAKaBAUIO AeHEHHE, Hamp. Geta aroHHCTH c npoMBMRWTeAKO AeHicTBHe, MYKONHTHUN H aHTHEHOTHUA. amipagoctostioro eocTomHiNe (OBOCTpAHHA “1pe2 BBNPOCHHK 3a pecTIMparopim H CHCTEMHH CHM kauecT#o Ha xHBOT ‘pes BLNPOCHHK a KHCTO3Ha GHOpO.A) He ce HaBHOAABA, 16‘TaGauua 4: anamrupana cpequa pasta OT rmaue6o sa a6comorHa NpoMsHa OT H3XOMHNTe CTOHHOCTH CHIEN. 12 ceammun ‘Onall ‘asa itl Bevan autem Bewinwnaument | < 11 roamin | 212 ronmnn (Nearpana = 176, (Nome = 293, Nompuea = ‘Neaaeso™ 168) Numeto = 147) 198, Nesmeo = 100) cpeaso] p> | epeao |p| epesno =peauo (95% CI) | crown | (95%CI) | ero | OS%CH | 5%CD ocr ocr OEOAUCH Cor 3.39 or 0.63 2.58 nnpenaunenoro)* <0.001| 0.27, | 0.092 ceamene (167, 5.12) G5) (-458,3.32) | (0.50, 4.65) pasa @EO,AUCaa (apn) 0.09 007 0.01 0.0 abcoxamna (0.03, 0.14) | -" | (.02, 0.12) |! | 0.07, 0.08) | (0.03,0.17) npowsna Halt —nncxa crofinocr ®EO; i i Cor 222 1 “124 2 npeaswxenoro)* | (038, 4.06) | °°'8 | 50,330 | 5 | ¢5.20,-271) | (0.49, 462) abconomna npowsna Hatl-iiexa Comet PEO! 006 | gore | 997 | oor2 | Ot 0.10 eee (0.01, 0.11) (0.02, 0.12) (0.08, 0.06) | (0.03, 0.17) npomana *Ko-mepnra ype un Bowuku nexenaHu nekapcrBenu peakupu (HIP) aSmogasani pH npoy'saHHaTa 3a KHCTOsHA dbHGposa ca vaRecTHH Heakenann esjekra Ha THOTpONMyM (1x. 4.8). Hal-vecTo HaGmodasanWTe HexenaHH CHOTA, KOMTO ce paataekaar KaTo cHMpsann mpes 12-cemmHueus asoiiHo-cnan nepwon ca KauizHua (4.1%) cyxora p yerara (2.8%). Bpost u npouenrsr naywenrs, kowTo choGuaBar aa HexesaHH CHOuTHA (HC) oT ceunaten MiTTepeC MH ucToaHara uGpona, HesaBCHMO OT BIRKMOBpEsKaTa, ca noKasaHH 8 TaOnaua 5. TIpHsHau # CHMITTOME, korrTo ce pasrnexaT KATO NpomeM Ha KHCTO3Ha HOposA ce YREAHYABAT HUCEHO C THOTPONMYM, BEER, Ne He € CTATHCTHMeCKH 3HAHAMO, OcOGEHO NpH NauMeHTH 80 ml/min). Tipu nauesrr ¢ XOBB, crpaaauie ot ymepero 20 TexKo GsGpeuno Hapyientie (CLcx <50 mI/min), ene HirTpaneHosHo MprvIOKeHHE Ha enHOKparita 2032 THOTPONHyM ce HaSmOARBA YaBOABANE Ha OOUATA exerroamus (82 % nosHutenie 8 AUCoar H 52% nosntuerne Ha Cass) 8 cpanienne c nauseuTH c XOBB ¢ Hopmaiua Ge6peuna GyHKIUL, KETO € GHIO NoTEEPACHO OT THA3MeHHTe KOHUCHTPALIMH CAEN HEXANATOPHO Npuioxenne wa Mpax 38 HiXATAAS, Tipu nawerrrure ¢ acta H s1eKo 6z6peuHo yaperknaste (CLcr 50-80 ml/min) ayxanaTopunst He BogH 0 SHANHMO NOBHUeHHe Ha eKCTOSHINAATA B cPpaBHeHNe ¢ nBuMeHTH C HOpwasiia ymeuas, a