{"id":1038,"date":"2017-01-30T20:12:06","date_gmt":"2017-01-30T19:12:06","guid":{"rendered":"http:\/\/www.newslab.sk\/2017\/01\/30\/plucna-aspergiloza\/"},"modified":"2017-10-03T09:31:27","modified_gmt":"2017-10-03T07:31:27","slug":"pulmonary-aspergillosis","status":"publish","type":"post","link":"https:\/\/www.newslab.sk\/en\/pulmonary-aspergillosis\/","title":{"rendered":"Pulmonary aspergillosis"},"content":{"rendered":"
*All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf\u00a0\r\nattachment at the end of the paper.<\/strong><\/span><\/pre>\n
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V posledn\u00fdch \u00a0rokoch sa roz\u0161iruje spektrum etiologick\u00fdch agensov infekci\u00ed z d\u00f4vodu narastaj\u00faceho po\u010dtu imunokompromitovan\u00fdch jedincov lie\u010den\u00fdch agres\u00edvnymi chemoterapeutikami, a tie\u017e v\u010faka zlep\u0161uj\u00facim sa mo\u017enostiam diagnostiky. Do popredia sa dost\u00e1vaj\u00fa tie\u017e mikroskopick\u00e9 huby \u2013 kvasinky a vl\u00e1knit\u00e9 huby (1, 2). Z\u00e1stupcovia rodu A<\/em>s<\/em>p<\/em>ergillus \u00a0<\/em>sa be\u017ene vyskytuj\u00fa v prostred\u00ed. Vstupnou br\u00e1nou infekcie s\u00fa d\u00fdchacie cesty, pacient sa nakaz\u00ed inhal\u00e1ciou sp\u00f3r (kon\u00eddi\u00ed) (3). Kon\u00eddie sa v\u010faka svojej malej ve\u013ekosti m\u00f4\u017eu dosta\u0165 a\u017e do p\u013e\u00facnych alveol, v ktor\u00fdch za vhodn\u00fdch pod- mienok kl\u00ed\u010dia a prerastaj\u00fa vo forme myc\u00e9lia (sple\u0165 h\u00fdf \u2013 hubov\u00fdch vl\u00e1ken) cez okolit\u00e9 \u0161trukt\u00fary, pr\u00edpadne \u00a0a\u017e do krvn\u00e9ho obehu, a tak do \u010fal\u0161\u00edch org\u00e1nov. Predilek\u010dnou lokaliz\u00e1ciou aspergil\u00f3zy s\u00fa p\u013e\u00faca (4). Mimop\u013e\u00facna lokaliz\u00e1cia je vz\u00e1cnej\u0161ia (paranaz\u00e1lne dutiny, obli\u010dky, mozog, pe\u010de\u0148, ko\u017ea). Naj\u010dastej\u0161\u00edm p\u00f4vodcom \u00a0hum\u00e1nnych \u00a0aspergil\u00f3z je A<\/em>s<\/em>p<\/em>ergillus <\/em>f<\/em>umigatus <\/em>(5), nasledovan\u00fd \u00a0druhmi \u00a0A<\/em>. flavus<\/em>, A<\/em>. niger <\/em>a A<\/em>. terreus \u00a0<\/em>(6, 7).<\/p>\n
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Formy p\u013e\u00facnej aspergil\u00f3zy<\/strong><\/p>\n
Invaz\u00edvna p\u013e\u00facna aspergil\u00f3za (IPA)<\/em><\/p>\n
T\u00e1to najz\u00e1va\u017enej\u0161ia forma p\u013e\u00facnej aspergil\u00f3z y (PA) sa v ysk y tuje predov\u0161etk\u00fdm \u00a0u v\u00fdrazne imunitne oslaben\u00fdch jedincov. Letalita IPA sa pohybuje od 50 % a\u017e do 90 % (5). Najviac ohrozen\u00ed \u00a0s\u00fa pacienti s dlhodobou neutrop\u00e9niou, ak\u00fatnou leuk\u00e9miou, po transplant\u00e1cii krvotvorn\u00fdch buniek a org\u00e1nov (srdce, p\u013e\u00faca, pe\u010de\u0148, obli\u010dky), dlhodobo lie\u010den\u00ed kor tikosteroidmi alebo imunosupres\u00edvami \u00a0(7, 8). V klinickom obraze dominuje \u00a0hor\u00fa\u010dka, \u00a0neprodukt\u00edvny \u00a0dr\u00e1\u017ediv \u00fd ka\u0161e\u013e, dyspnoe, pleur\u00e1lna boles\u0165, pleur\u00e1lny trec\u00ed \u0161elest (8, 9). N\u00e1sledkom \u00a0angioinvazivity je hemopt\u00fdza, pri mas\u00edvnej\u0161om postihnut\u00ed vznikaj\u00fa kavit\u00e1cie. M\u00f4\u017ee d\u00f4js\u0165 k disemin\u00e1cii \u00a0\u2013 najm\u00e4 do CNS (centr\u00e1lny nervov\u00fd syst\u00e9m), \u010do sa sp\u00e1ja s ve\u013emi nepriaznivou progn\u00f3zou\u00a0 (3). V z\u00e1va\u017en\u00fdch pr\u00edpadoch prib\u00fadaj\u00fa zn\u00e1mky konsolid\u00e1cie p\u013e\u00fac, tachypnoe, progres\u00edvne sa zhor\u0161uj\u00faca hypox\u00e9mia a\u017e respira\u010dn\u00e9 zlyhanie. Na \u00faspe\u0161n\u00e9 zvl\u00e1dnutie IPA je nevyhnutn\u00e9 v\u010dasn\u00e9 stanovenie diagn\u00f3zy a najm\u00e4 pod\u00e1vanie \u00fa\u010dinnej antimykotickej (ATM) lie\u010dby (7, 9). V s\u00fa\u010dasnosti \u00a0je liekom vo\u013eby vorikonazol, v druhej l\u00ednii lipidov\u00fd komplex \u00a0amfoteric\u00ednu \u00a0B, posakonazol \u00a0alebo kaspofung\u00edn (8). Niekedy je potrebn\u00e1 aj chirurgick\u00e1 intervencia (6).<\/p>\n
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Chronick\u00e1 nekrotizuj\u00faca p\u013e\u00facna aspergil\u00f3za (CNPA)<\/em><\/p>\n
T\u00e1to vz\u00e1cna chronick\u00e1 infekcia je takmer v\u017edy sp\u00f4soben\u00e1 druhom A<\/em>. fumigatus <\/em>(5). Ide o lok\u00e1lnu inv\u00e1ziu h\u00fdf do p\u013e\u00facneho parench\u00fdmu, bez angioinvazivity a disemin\u00e1cie do in\u00fdch org\u00e1nov, pri ktorej doch\u00e1dza k nekr\u00f3zam a z\u00e1palu. CNPA sa vyskytuje najm\u00e4\u00a0 u star\u0161\u00edch pacientov s chronick\u00fdmi p\u013e\u00facnymi ochoreniami (chronick\u00e1 ob\u0161truk\u010dn\u00e1 p\u013e\u00facna choroba, p\u013e\u00facna tuberkul\u00f3za, pneumokoni\u00f3za, \u00a0cystick\u00e1 fibr\u00f3za, sarkoid\u00f3za, p\u013e\u00facny infarkt) a nezriedka aj s miernym imunodeficitom \u010di chronick\u00fdm alkoholizmom (3).<\/p>\n
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P\u013e\u00facny aspergil\u00f3m<\/em><\/p>\n
Aspergil\u00f3m (mycet\u00f3m) \u00a0je gu\u013eovit\u00fd \u00fatvar tvoren\u00fd masou h\u00fdf, hlienu, fibr\u00ednu a leukocytov. Vytv\u00e1ra sa v preexistuj\u00facej dutine p\u013e\u00facneho \u00a0parench\u00fdmu. Naj\u010dastej\u0161ou \u00a0pr\u00ed\u010dinou \u00a0vzniku t\u00fdchto dut\u00edn je tuberkul\u00f3za, sarkoid\u00f3za, in\u00fd nekrotizuj\u00faci p\u013e\u00facny proces (absces, in\u00e9 p\u013e\u00facne infekcie), cystick\u00e1 fibr\u00f3za alebo n\u00e1dor (3, 5). Aspergil\u00f3m \u00a0len zriedkavo men\u00ed svoju ve\u013ekos\u0165 a pri po\u0161koden\u00ed ciev v bezprostrednej bl\u00edzkosti m\u00f4\u017ee sp\u00f4sobi\u0165 krv\u00e1canie. Definit\u00edvnou lie\u010dbou je chirurgick\u00e9 rie\u0161enie \u2013 resekcia aspergil\u00f3mu alebo cielen\u00e1 emboliz\u00e1cia vy\u017eivovacej bronchi\u00e1lnej art\u00e9rie.<\/p>\n
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Alergick\u00e1 bronchopulmon\u00e1lna aspergil\u00f3za (ABPA)<\/em><\/p>\n
T\u00e1to forma aspergil\u00f3zy sa vyskytuje predov\u0161etk\u00fdm u pacientov s priedu\u0161kovou astmou alebo cystickou fibr\u00f3zou a v\u00fdrazne zhor\u0161uje priebeh t\u00fdchto ochoren\u00ed \u00a0(3). ABPA predstavuje hypersenzit\u00edvnu \u00a0reakciu na koloniz\u00e1ciu d\u00fdchac\u00edch ciest A<\/em>s<\/em>p<\/em>e<\/em>r<\/em>g<\/em>i<\/em>ll<\/em>u<\/em>s <\/em>spp. <\/em>Doch\u00e1dza k upchatiu d\u00fdchac\u00edch ciest zhlukom \u00a0hlienu, \u00a0h\u00fdf, z\u00e1palov\u00fdch \u00a0buniek, bez po\u0161kodzovania p\u013e\u00facneho tkaniva (5). Priebeh \u00a0ochorenia \u00a0je mo\u017en\u00e9 lie\u010debne ovplyvni\u0165 celkov\u00fdmi kortikoidmi a v niektor\u00fdch pr\u00edpadoch pridan\u00edm ATM (3).<\/p>\n
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Di<\/strong>a<\/strong>g<\/strong>nos<\/strong>t<\/strong>ik<\/strong>a p\u013e \u00facnej aspergil\u00f3zy<\/strong><\/p>\n
Diagnostika p\u013e\u00facnej \u00a0aspergil\u00f3zy je interdisciplin\u00e1rny proces. Opiera sa o klinick\u00fd obraz, zobrazovacie met\u00f3dy a laborat\u00f3rne vy\u0161etrenia. HRCT (hig<\/em>h-resolution computed tomography <\/em>\u2013 po\u010d\u00edta\u010dov\u00e1 tomografia s vysok\u00fdm rozl\u00ed\u0161en\u00edm) m\u00e1 v porovnan\u00ed s klasick\u00fdm RTG vy\u0161etren\u00edm ove\u013ea v\u00e4\u010d\u0161\u00ed pr\u00ednos v diagnostike. Pri IPA sa stret\u00e1vame \u00a0s r\u00f4znorod\u00fdmi n\u00e1lezmi \u2013 mnohopo\u010detn\u00e9 \u00a0lo\u017eisk\u00e1, kavit\u00e1cie, pleur\u00e1lny \u00a0v\u00fdpotok, \u201eg<\/em>r<\/em>o<\/em>und<\/em> g<\/em>lass <\/em>op<\/em>a<\/em>c<\/em>i<\/em>t<\/em>y<\/em>\u201c (obraz mlie\u010dneho skla), \u201e<\/em>h<\/em>alo sign\u201c <\/em>(prekrv\u00e1canie \u00a0na perif\u00e9rii centr\u00e1lnej kondenz\u00e1cie) alebo \u201e<\/em>air crescent <\/em>s<\/em>i<\/em>g<\/em>n<\/em>\u201c (rozpadov\u00e1 dutina).<\/p>\n
\u010eal\u0161\u00edm krokom by mali by\u0165 mikrobiologick\u00e9 anal\u00fdzy: stanovenie galaktoman\u00e1nu (GM) v BAL (bronchoalveol\u00e1rna lav\u00e1\u017e) a krvnom s\u00e9re, mikroskopick\u00e1 a kultiva\u010dn\u00e1 anal\u00fdza BAL (9, 10, 11, 12, 13).<\/p>\n
Mozaiku vy\u0161etren\u00ed m\u00f4\u017ee doplni\u0165 d\u00f4kaz DNA (de<\/em>o<\/em>x<\/em>yri<\/em>bonucleic <\/em>a<\/em>c<\/em>i<\/em>d\u00a0<\/em>\u2212 deoxyribonukleov\u00e1 kyselina) A<\/em>s<\/em>pergillus \u00a0<\/em>spp. met\u00f3dou PCR (polymerase chain reaction <\/em>\u2013 polymer\u00e1zov\u00e1 re\u0165azov\u00e1 reakcia) vo vzork\u00e1ch BAL, krvi a in\u00fdch prim\u00e1rne steriln\u00fdch biologick\u00fdch \u00a0materi\u00e1loch (8, 9, 10). N\u00e1pomocnou met\u00f3dou je tie\u017e detekcia 1,3-\u03b2<\/em>-D-gluk\u00e1nu (BDG), najm\u00e4 vo vzork\u00e1ch krvn\u00e9ho s\u00e9ra (v\u00fdnimo\u010dne aj v BAL). Jednou z mo\u017enost\u00ed je histologick\u00e9 vy\u0161etrenie vzoriek z\u00edskan\u00fdch biopsiou p\u013e\u00facnych infiltr\u00e1tov, av\u0161ak pre vysok\u00e9 riziko komplik\u00e1ci\u00ed a \u010dast\u00fa kontraindik\u00e1ciu v\u00fdkonu sa t\u00e1to mo\u017enos\u0165 \u0161ir\u0161ie nevyu\u017e\u00edva.<\/p>\n
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M<\/strong>i<\/strong>k<\/strong>r<\/strong>o<\/strong>b<\/strong>i<\/strong>olog<\/strong>i<\/strong>c<\/strong>k<\/strong>\u00e1 diagnostika PA<\/strong><\/p>\n
Pri podozren\u00ed \u00a0na p\u013e\u00facnu aspergil\u00f3zu sa odpor\u00fa\u010da \u00a0zasla\u0165 biologick\u00fd materi\u00e1l cielene \u00a0do mykologick\u00e9ho laborat\u00f3ria. Medzi \u00a0diagnosticky najpr\u00ednosnej\u0161ie vzorky patr\u00ed BAL, bioptick\u00e1 vzorka p\u013e\u00fac, krvn\u00e9 s\u00e9rum, punkt\u00e1ty z prim\u00e1rne steriln\u00fdch lokal\u00edt a pri podozren\u00ed na disemin\u00e1ciu do CNS aj likvor. Menej vhodn\u00fdm materi\u00e1lom je odsat\u00fd sekr\u00e9t (OS) z doln\u00fdch d\u00fdchac\u00edch ciest (DDC) alebo sp\u00fatum. Pozit\u00edvny n\u00e1lez v t\u00fdchto biologick\u00fdch materi\u00e1loch m\u00f4\u017ee by\u0165 sp\u00f4soben\u00fd koloniz\u00e1ciou d\u00fdchac\u00edch ciest.<\/p>\n
Mikroskopia je \u010dasovo nen\u00e1ro\u010dn\u00e1, ale vy\u017eaduje si sk\u00fasenos\u0165 mykol\u00f3ga (1, 9). Pr\u00edtomnos\u0165 \u00a0h\u00fdf v biologickom \u00a0materi\u00e1li z DDC zvy\u0161uje pravdepodobnos\u0165 mo\u017enej p\u013e\u00facnej aspergil\u00f3zy. Senzitivita mikroskopie s\u00edce v\u00fdrazne kol\u00ed\u0161e (0 % a\u017e 90 %) (10), ale pr\u00edtomnos\u0165 elementov mikroskopick\u00fdch h\u00fab vo vzorke m\u00f4\u017ee \u00a0klinikov nasmerova\u0165 \u00a0k mykotickej etiol\u00f3gii infekcie. Nev\u00fdhodou \u00a0tejto anal\u00fdzy okrem \u00a0n\u00edzkej senzitivity je, \u017ee neumo\u017e\u0148uje identifikova\u0165 p\u00f4vodcu \u00a0do rodu a druhu. H\u00fdfy A<\/em>s<\/em>p<\/em>ergillus <\/em>spp. sa nedaj\u00fa spo\u013eahlivo odl\u00ed\u0161i\u0165 od h\u00fdf niektor\u00fdch \u010fal\u0161\u00edch rodov mikromyc\u00e9t \u00a0(9, 10, 13).<\/p>\n
Kultiv\u00e1cia vl\u00e1knit\u00fdch h\u00fab je \u010dasovo n\u00e1ro\u010dn\u00e1 (2 a\u017e 14 dn\u00ed), av\u0161ak pozit\u00edvny n\u00e1lez umo\u017e\u0148uje ur\u010di\u0165 mo\u017en\u00e9ho p\u00f4vodcu infekcie (1, 2). Nev\u00fdhodou kultiv\u00e1cie je okrem d\u013a\u017eky jej trvania tie\u017e n\u00edzka senzitivita \u2013 okolo 50 % (9), \u010do m\u00f4\u017ee s\u00favisie\u0165 s predo\u0161lou ATM lie\u010dbou pacienta a faktom, \u017ee elementy mikroskopick\u00fdch h\u00fab nemusia by\u0165 vo vzorke rovnomerne rozpt\u00fdlen\u00e9. Pokia\u013e sa A<\/em>s<\/em>p<\/em>ergillus <\/em>sp. vykultivuje z bioptickej vzorky tkaniva, diagn\u00f3za aspergil\u00f3zy \u00a0je potvrden\u00e1 \u00a0(10). Z\u00e1kladn\u00fdm \u00a0kultiva\u010dn\u00fdm \u00a0m\u00e9diom \u00a0je Sabouraudov \u00a0gluk\u00f3zov\u00fd agar. Z narastenej kult\u00fary (obr\u00e1zok 1) sa zhotov\u00ed prepar\u00e1t, napr\u00edklad v laktofenole s bavln\u00edkovou \u00a0modrou \u00a0(obr\u00e1zok\u00a0 2). Na z\u00e1klade makro- a mikromorfol\u00f3gie sa izol\u00e1t identifikuje na \u00farove\u0148 druhu (respekt\u00edve sekcie alebo len rodu). Kvantitat\u00edvna citlivos\u0165 kme\u0148a na ATM sa stanovuje formou E-testu. V\u00fdsledkom je \u010d\u00edseln\u00fd \u00fadaj v jednotke mg\/l, ktor\u00fd predstavuje hodnotu MIC (minimu<\/em>m inhibitory concentration <\/em>\u2013 minim\u00e1lna inhibi\u010dn\u00e1 koncentr\u00e1cia) dan\u00e9ho ATM pre konkr\u00e9tny izol\u00e1t A<\/em>s<\/em>p<\/em>ergillus \u00a0<\/em>sp. (obr\u00e1zok 3). \u0160tandardnou \u00a0p\u00f4dou \u00a0na stanovenie citlivosti vl\u00e1knit\u00fdch h\u00fab na ATM je RPMI m\u00e9dium (Roswell Park Memorial \u00a0Institute <\/em>m<\/em>e<\/em>d<\/em>i<\/em>u<\/em>m<\/em>). Pod\u013ea Vestn\u00edka Ministerstva zdravotn\u00edctva Slovenskej republiky z roku 2010 sa odpor\u00fa\u010da \u00a0stanovova\u0165 citlivos\u0165 na vorikonazol, amfoteric\u00edn B, posakonazol, kaspofung\u00edn a itrakonazol (14).<\/p>\n
Stanovenie GM v BAL a kr vnom s\u00e9re met\u00f3dou \u00a0ELISA (e<\/em>n<\/em>z<\/em> y<\/em>m<\/em>e<\/em>lin<\/em>k<\/em>e<\/em>d immunosorbent <\/em>as<\/em>s<\/em>a<\/em>y <\/em>\u2013 imunoenz ymatick\u00e1 anal\u00fdza na d\u00f4kaz antig\u00e9nov alebo protil\u00e1tok) sa stalo jedn\u00fdm z k\u013e\u00fa\u010dov\u00fdch laborat\u00f3rnych vy\u0161etren\u00ed pri podozren\u00ed na IPA (7, 15). Tento antig\u00e9n sa uvo\u013e\u0148uje z bunkovej steny niektor\u00fdch mikroskopick\u00fdch h\u00fab (vr\u00e1tane druhov rodu A<\/em>s<\/em>p<\/em>e<\/em>r<\/em>gill<\/em>us<\/em>) po\u010das ich rastu. Mno\u017estvo \u00a0GM vo vzorke sa vyjadruje pomocou indexu pozitivit y (IP), ktor\u00fd m\u00e1 r\u00f4zne hrani\u010dn\u00e9 hodnoty (c<\/em>u<\/em>t<\/em>–<\/em>o<\/em>f<\/em> f <\/em>) v biologick \u00fdch materi\u00e1loch BAL a s\u00e9rum. Vo vzork\u00e1ch BAL je cu<\/em>t<\/em>–<\/em>o<\/em>f<\/em>f \u00a0<\/em>IP = 1,0 (11, 15). V krvnom s\u00e9re je GM negat\u00edvny \u00a0pri IP < 0,5; slabo pozit\u00edvny od IP \u2265 0,5 a\u017e do < 0,7 a pozit\u00edvny \u00a0pri IP \u2265 0,7. N\u00e1lez \u00a0IP GM \u2265 0,5 v dvoch za sebou nasleduj\u00facich \u00a0vzork\u00e1ch je mikrobiologick\u00fdm krit\u00e9riom pre pravdepodobn\u00fa aspergil\u00f3zu (9). Pri detekcii GM je \u010dasto pozorovan\u00e1 skr\u00ed\u017een\u00e1 (falo\u0161n\u00e1) pozitivita. Je opisovan\u00e1 pri syst\u00e9mov\u00fdch infekci\u00e1ch vyvolan\u00fdch in\u00fdmi rodmi mikroskopick \u00fdch h\u00fab (P<\/em>e<\/em>nicilliu<\/em>m <\/em>spp., Paecilomyces \u00a0<\/em>spp., Alternaria <\/em>spp., Rhodotorula \u00a0<\/em>spp., <\/em>H<\/em>i<\/em>s<\/em>toplasma capsulatum<\/em>), lie\u010dbe pacientov niek tor \u00fdmi betalak t\u00e1mov\u00fdmi antibiotikami (ampicil\u00edn, \u00a0ampicil\u00edn\/sulbak t\u00e1m, \u00a0piperacil\u00edn\/tazobak t\u00e1m, amoxicil\u00edn\/ \u00a0klavulan\u00e1t), koloniz\u00e1cii \u010drevnej sliznice B<\/em>i<\/em>f<\/em>i<\/em>doba<\/em>c<\/em>terium <\/em>spp. \u00a0u novorodencov \u00a0(najm\u00e4 nedonosen\u00fdch), \u00a0prieniku GM z niektor\u00fdch mlie\u010dnych v\u00fdrobkov cez po\u0161koden\u00fa stenu gastrointestin\u00e1lneho traktu (mukozit\u00edda pri \u010drevnej GvHD, g<\/em>r<\/em>a<\/em>f<\/em>t<\/em>–<\/em>versus-host disease <\/em>\u2013 reakcia \u0161tepu vo\u010di hostite\u013eovi po transplant\u00e1cii), aplik\u00e1cii roztoku Plasmalyte<\/em>\u00ae, kontamin\u00e1cii vzorky po\u010das odberu alebo pri spracovan\u00ed materi\u00e1lu (vata, vzdu\u0161n\u00e9 kon\u00eddie A<\/em>s<\/em>p<\/em>e<\/em>r<\/em>gill<\/em>us\u00a0 <\/em>spp., P<\/em>e<\/em>nicilliu<\/em>m <\/em>spp.) (9, 10, 16). Pozitivita GM v BAL pri p\u013e\u00facnej aspergil\u00f3ze m\u00f4\u017ee \u010dasovo predch\u00e1dza\u0165\u00a0 jeho pozitivitu v krvnom s\u00e9re (9), preto \u00a0sa pri podozren\u00ed \u00a0na IPA odpor\u00fa\u010da v\u010das odobra\u0165 BAL na stanovenie GM. V\u00fdhodou vy\u0161etrenia hladiny GM (predov\u0161etk\u00fdm v BAL) je jeho vysok\u00e1 senzitivita a \u0161pecifickos\u0165 (61 % a\u017e 94 % a 71 % a\u017e 92 %) (10), ako aj negat\u00edvna \u00a0predikt\u00edvna hodnota \u00a0(92 % a\u017e 98 %) (5), pri\u010dom \u00a0vy\u0161\u0161ie hodnoty sa zaznamenali pri vy\u0161etren\u00ed BAL (10). Monitorovanie \u00a0hodn\u00f4t \u00a0IP GM je jedn\u00fdm \u00a0z ukazovate\u013eov \u00faspe\u0161nosti ATM lie\u010dby pacienta s IPA.<\/p>\n
 <\/p>\n
Protil\u00e1tky vo\u010di A<\/em>. fumigatus <\/em>sa stanovuj\u00fa z krvn\u00e9ho \u00a0s\u00e9ra, napr\u00edklad nepriamou hemaglutin\u00e1ciou \u00a0(celkov\u00e9 protil\u00e1tky) alebo met\u00f3dou \u00a0ELISA\u2013 \u0161pecifick\u00e9 protil\u00e1tky tried IgA, IgM a IgG, respekt\u00edve \u00a0IgE. Pri nepriamej hemaglutina\u010dnej met\u00f3de sa ako hrani\u010dn\u00fd titer protil\u00e1tok ud\u00e1va hodnota 1 : 320. \u00a0V takom pr\u00edpade sa odpor\u00fa\u010da \u00a0opakova\u0165 vy\u0161etrenie s odstupom 2 a\u017e 3 t\u00fd\u017ed\u0148ov. Signifikantn\u00fa reakciu v zmysle aspergil\u00f3zy predstavuje \u00a0titer \u2265 1 : \u00a0640. \u00a0V\u00fdhodou t\u00fdchto s\u00e9rologick \u00fdch anal\u00fdz je vyu\u017eitie ich stanovenia \u00a0pri diagnostike ABPA, \u00a0CNPA alebo p\u013e\u00facneho aspergil\u00f3mu.<\/p>\n
Pri diagnostike \u00a0IPA je mo\u017en\u00e9 vyu\u017ei\u0165 aj stanovenie \u00a0BDG (9, 10, 17). Tento antig\u00e9n sa uvo\u013e\u0148uje do krvn\u00e9ho obehu pri akt\u00edvne prebiehaj\u00facej syst\u00e9movej myk\u00f3ze, a to nielen pri aspergil\u00f3ze, ale aj pri infekcii vyvolanej in\u00fdmi mikroskopick\u00fdmi hubami \u00a0\u2013 s v\u00fdnimkou mukormyc\u00e9t \u00a0a druhov rodu C<\/em>r<\/em>y<\/em>p<\/em>t<\/em>o<\/em>c<\/em>o<\/em>c<\/em>c<\/em>u<\/em>s \u00a0<\/em>(9). Ni\u017e\u0161ia \u0161pecifickos\u0165 \u00a0(76 %) je jednou \u00a0z nev\u00fdhod tohto laborat\u00f3rneho testu (15). Falo\u0161ne pozit\u00edvny n\u00e1lez bol pozorovan\u00fd u pacientov lie\u010den\u00fdch niektor\u00fdmi antibiotikami (amoxicil\u00edn\/klavulan\u00e1t, imipen\u00e9m, gentamic\u00edn), pri dial\u00fdze s pou\u017eit\u00edm celul\u00f3zovej membr\u00e1ny, kontamin\u00e1cii g\u00e1zou, bakteri\u00e1lnej sepse alebo laborat\u00f3rnej kontamin\u00e1- cii (9). Silnou \u00a0str\u00e1nkou \u00a0tejto \u00a0met\u00f3dy \u00a0je vysok\u00e1 negat\u00edvna \u00a0predikt\u00edvna hodnota \u00a0(94 %) (15).<\/p>\n
Met\u00f3dy molekul\u00e1rnej biol\u00f3gie sa vyu\u017e\u00edvaj\u00fa \u010doraz \u010dastej\u0161ie. Pri podozren\u00ed na IPA sa stanovuje pr\u00edtomnos\u0165 DNA A<\/em>s<\/em>p<\/em>ergillus <\/em>spp. v biologick\u00fdch vzork\u00e1ch PCR anal\u00fdzami. K dispoz\u00edcii je nieko\u013eko komer\u010dn\u00fdch \u00a0s\u00faprav na r\u00f4zne typy PCR reakci\u00ed a pod\u013ea viacer\u00fdch \u0161t\u00fadi\u00ed sa dosahuj\u00fa dobr\u00e9 v\u00fdsledky z h\u013eadiska senzitivity (70 % a\u017e 91 %), \u0161pecifickosti (97 % a\u017e 100 %), pozit\u00edvnej (100 %) a negat\u00edvnej predikt\u00edvnej hodnoty \u00a0(93 %) (10, 15). St\u00e1le v\u0161ak ch\u00fdba \u0161tandardiz\u00e1cia t\u00fdchto anal\u00fdz pre rutinn\u00e9 laborat\u00f3rne vy\u0161etrenie. Pozit\u00edvny PCR n\u00e1lez u imunokompromitovan\u00e9ho \u00a0symptomatick\u00e9ho pacienta m\u00e1 vysok\u00fa diagnostick\u00fa hodnotu. Molekul\u00e1rno-biologick\u00e9 stanovenia s\u00fa v\u0161ak vysoko senzit\u00edvne, preto m\u00f4\u017ee \u013eahko d\u00f4js\u0165 k falo\u0161ne pozit\u00edvnym v\u00fdsledkom, napr\u00edklad pri kontamin\u00e1cii vzorky kon\u00eddiami A<\/em>s<\/em>p<\/em>ergillus \u00a0<\/em>spp. z prostredia alebo pri koloniz\u00e1cii DDC.<\/p>\n
Interpret\u00e1cia v\u00fdsledkov mykologick\u00fdch vy\u0161etren\u00ed je n\u00e1ro\u010dn\u00e1 a odpor\u00fa\u010da sa pod\u013ea mo\u017enosti potvrdi\u0165 n\u00e1lez opakovan\u00fdm vy\u0161etren\u00edm.<\/p>\n
Odb<\/strong>e<\/strong>r a transport biologick\u00e9ho materi\u00e1lu<\/strong><\/p>\n
Biologick\u00fd materi\u00e1l je potrebn\u00e9 odobera\u0165 asepticky do steriln\u00fdch uzatv\u00e1rate\u013en\u00fdch odberov\u00fdch n\u00e1dob a po odbere ich u\u017e neotv\u00e1ra\u0165. V\u0161eobecne plat\u00ed, \u017ee materi\u00e1l by mal by \u0165 doru\u010den\u00fd do laborat\u00f3ria \u010do najsk\u00f4r po odbere \u2013 pri diagnostike \u00a0PA cielene na oddelenie mykol\u00f3gie. Rovnako d\u00f4le\u017eit\u00e9 je spr\u00e1vne a \u010ditate\u013ene vyplni\u0165 mikrobiologick\u00fa (mykologick\u00fa) \u017eiadanku vr\u00e1tane uvedenia adekv\u00e1tnej diagn\u00f3zy. Identifika\u010dn\u00e9 \u00fadaje pacienta \u00a0(meno, \u00a0rodn\u00e9 \u010d\u00edslo), typ materi\u00e1lu a po\u017eadovan\u00fdch \u00a0anal\u00fdz je potrebn\u00e9 \u00a0zazna\u010di\u0165 aj na odberovej n\u00e1dobe (sk\u00famavke, tamp\u00f3ne).<\/p>\n
Materi\u00e1l z\u00edskan\u00fd pri bronchoskopii \u00a0(BAL) a bioptick\u00e9 vzorky sa uscho- v\u00e1vaj\u00fa v sterilnom fyziologickom roztoku. Sp\u00fatum sa odober\u00e1 r\u00e1no pri prvej expektor\u00e1cii po vypl\u00e1chnut\u00ed \u00fastnej dutiny \u010distou pitnou vodou.<\/p>\n
Na stanovenie s\u00e9rov\u00e9ho GM a protil\u00e1tok vo\u010di A<\/em>. fumigatus \u00a0<\/em>sa odober\u00e1 krv do sk\u00famavky s g\u00e9lom (respekt\u00edve do sk\u00famavky bez protizr\u00e1\u017eav\u00e9ho \u010dinidla) s objemom \u00a0minim\u00e1lne 2 a\u017e 3 ml. Pri mo\u017enosti \u00a0transportu materi\u00e1lu do 2 hod\u00edn od odberu sa m\u00f4\u017ee skladova\u0165 pri izbovej teplote (+18 \u00b0C a\u017e +25 \u00b0C). Ak je predpokladan\u00e1 lehota doru\u010denia vzorky 2 a\u017e 24 hod\u00edn, je potrebn\u00e9 \u00a0uschova\u0165 \u00a0ju pri teplote +2 \u00b0C a\u017e +8 \u00b0C. Pri dlh\u0161om skladovan\u00ed je potrebn\u00e9 oddeli\u0165 krvn\u00e9 s\u00e9rum (v lamin\u00e1rnom boxe, aby sa minimalizovalo \u00a0riziko kontamin\u00e1cie \u00a0vzorky) a zamrazi\u0165 ho na -18 \u00b0C a\u017e -24 \u00b0C.<\/p>\n
Kultiv\u00e1cia spolu s mikroskopiou (pri po\u017eiadavke na kultiva\u010dn\u00e9 vy\u0161etrenie sa vykon\u00e1va automaticky) biologick\u00e9ho materi\u00e1lu sa realizuje denne. GM a celkov\u00e9 protil\u00e1tky vo\u010di A<\/em>. fumigatus <\/em>sa vy\u0161etruj\u00fa t. \u010d. 2-kr\u00e1t t\u00fd\u017edenne (utorky a piatky), pri\u010dom materi\u00e1l mus\u00ed by\u0165 doru\u010den\u00fd \u00a0do laborat\u00f3ria najnesk\u00f4r de\u0148 vopred.<\/p>\n
Stanovenie s\u00e9rov\u00e9ho galaktoman\u00e1nu a protil\u00e1tok vo\u010di A<\/em>. f<\/em>umigatus <\/em>je ur\u010den\u00e9 hospitalizovan\u00fdm pacientom, rovnako aj pacientom z hematoonkologick\u00fdch, imunoalergologick\u00fdch \u00a0a pneumologick\u00fdch \u00a0ambulanci\u00ed pri podozren\u00ed na niektor\u00fa z foriem p\u013e\u00facnej aspergil\u00f3zy. U ostatn\u00fdch ambulantn\u00fdch pacientov sa tieto anal\u00fdzy poskytuj\u00fa na priamu platbu (cenn\u00edk dostupn\u00fd na webovom rozhran\u00ed laborat\u00f3ri\u00ed).<\/p>\n
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Z<\/strong>\u00e1<\/strong>ver<\/strong><\/p>\n
P\u013e\u00facna aspergil\u00f3za si vy\u017eaduje n\u00e1le\u017eit\u00fa pozornos\u0165 pre svoj r\u00f4znorod\u00fd klinick\u00fd obraz, problematick\u00fa diagnostiku a v mnoh\u00fdch pr\u00edpadoch aj nepriazniv\u00fa \u00a0progn\u00f3zu. Z\u00e1kladom \u00faspe\u0161nej laborat\u00f3rnej diagnostiky IPA je v\u010dasn\u00e9 \u00a0rozpoznanie jej hrozby \u00a0na z\u00e1klade rizikov\u00fdch faktorov pacienta, ne\u0161pecifick\u00fdch klinick\u00fdch pr\u00edznakov a s pomocou \u010fal\u0161\u00edch vy\u0161etrovac\u00edch \u00a0met\u00f3d (9, 15). \u00a0V\u00fdsledky jednotliv\u00fdch laborat\u00f3rnych vy\u0161etren\u00ed je potrebn\u00e9 \u00a0interpretova\u0165 \u00a0v s\u00falade s klinick\u00fdm stavom pacienta, ako aj v\u00fdsledkami zobrazovac\u00edch met\u00f3d, \u010do predpoklad\u00e1 \u00fazku spolupr\u00e1cu \u00a0o\u0161etruj\u00facich \u00a0lek\u00e1rov a mikrobiol\u00f3gov \u00a0pri mana\u017emente pacienta s p\u013e\u00facnou aspergil\u00f3zou.<\/p>\n
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L<\/strong>it<\/strong>e<\/strong>ra<\/strong>t<\/strong>\u00fa<\/strong>ra<\/strong><\/p>\n
1<\/strong>. <\/strong>Buchta V, Hamal P, Mall\u00e1tov\u00e1 \u00a0N, et al. Nepodkro\u010diteln\u00e9 minimum laboratorn\u00ed diagnostiky invaz\u00edvn\u00edch mykotick\u00fdch infekc\u00ed \u2013 doporu\u010den\u00ed odborn\u00edk\u016f s podporou CELL a SLM JEP. P<\/em>ostgradu\u00e1ln\u00ed medic\u00edna<\/em>. 2010;12(p\u0159\u00edloha 5):76\u201381.<\/p>\n
2<\/strong>. <\/strong>To\u0161kov\u00e1 M, Winterov\u00e1 J, Kocmanov\u00e1 I, et al. Invaz\u00edvne mykotick\u00e9 infekcie u hematoonkologick\u00fdch pacientov \u2013 epidemiol\u00f3gia, rizikov\u00e9 faktory, klinick\u00e9 pr\u00edznaky a diagnostika. O<\/em>nko- logie<\/em>. 2012;6(6):298\u2013303<\/p>\n
3<\/strong>. <\/strong>Harman EM. A<\/em>spergillosis <\/em>[online]. Updated 2015. Available from: <http:\/\/emedicine.med<\/a>sc<\/span>ape.com\/article\/296052-overview>. Accessed December 28, 2015<\/p>\n
4<\/strong>. <\/strong>De Hoog GS, Guarro J, Gen\u00e9 J, et al. A<\/em>tlas of Clinical <\/em>F<\/em>ung<\/em>i<\/em>. 2nd ed. Utrecht, The Netherlands\/ Reus, Spain: Centraalbureau voor Schimmelcultures\/Universitat Rovira i Virgili; 2000: 1126<\/p>\n
5<\/strong>. <\/strong>Kousha M, Tadi R, Soubani AO. Pulmonary aspergillosis: a clinical review. E<\/em>u<\/em>r Respir Rev<\/em>. 2011;20(121):156\u2013174.<\/p>\n
6<\/strong>. <\/strong>Drgo\u0148a \u013d. Invaz\u00edvne mykotick\u00e9 \u00a0infekci In: Drgo\u0148a \u00a0\u013d. I<\/em>nfek\u010dn\u00e9 komplik\u00e1cie <\/em>o<\/em>nkologick\u00fdch pacientov<\/em>. Bratislava, Slovensk\u00e1 republika: Univerzita Komensk\u00e9ho; 2013: 24\u201342.<\/p>\n
7<\/strong>. <\/strong>Ga\u0161par M, Drgo\u0148a \u013d, P\u0151czov\u00e1 M, et al. V\u010dasn\u00e1 invaz\u00edvna p\u013e\u00facna aspergil\u00f3za s fat\u00e1lnym koncom u pacientky s ak\u00fatnou lymfoblastovou leuk\u00e9miou. O<\/em>nkol\u00f3gia <\/em>(<\/em>B<\/em>r<\/em>a<\/em>ti<\/em>s<\/em>l<\/em>.<\/em>)<\/em>. 2015;10(2):116\u2013120.<\/p>\n
8<\/strong>. <\/strong>Sherif R, Segal BH. Pulmonary Aspergillosis: clinical presentation, diagnostic tests, management and complications. C<\/em>ur<\/em>r Opin Pulm <\/em>M<\/em>e<\/em>d<\/em>. 2010 May;16(3):242\u2013250.<\/p>\n
9<\/strong>. <\/strong>The Czech Leukemia Study Group for Life (\u010cesk\u00e1 leukemick\u00e1 skupina \u2013 pro \u017eivot) \u2013 R\u00e1\u010dil Z, Mayer J, eds. Invazivn\u00ed aspergil\u00f3za: sou\u010dasn\u00e9 mo\u017enosti diagnostiky. V<\/em>nit<\/em>\u0159<\/em>. <\/em>L<\/em>\u00e9<\/em>k<\/em>. 2007;53(Suppl):S1\u2013S34.<\/p>\n
1<\/strong>0<\/strong>. <\/strong>Barton RC. Laboratory Diagnosis of Invasive Aspergillosis: From Diagnosis to Prediction of Outcom S<\/em>ci<\/em>e<\/em>n<\/em>tifi<\/em>c<\/em>a<\/em>. 2013;Article ID 459405:29.<\/p>\n
1<\/strong>1<\/strong>. <\/strong>Haber Hodnocen\u00ed galaktomananu v s\u00e9ru a bronchoalveol\u00e1rn\u00ed lav\u00e1\u017ei u neutropenick\u00fdch a non-neutropenick\u00fdch pacient\u016f. Kazuistiky <\/em>v alergologii, pneumologii a ORL<\/em>. 2011;8(2):10\u201313.<\/p>\n
1<\/strong>2<\/strong>. <\/strong>Sharma SK, Kumar S, Singh \u00a0AK, et al. Feasibility \u00a0and outcome \u00a0of CT-guided lung biopsy in patients with hematological \u00a0diseases and suspected \u00a0fungal pneumonia. J Infect Dev Ctries<\/em>. 2013;7(10):748\u2013752.<\/p>\n
1<\/strong>3<\/strong>. <\/strong>Crumley S, Hull A, Cernoch P, et al. Comparison between cytologic examination of fungi in bronchial washings and bronchoalveolar lavage specimens and culture: a review of 100 cases with emphasis \u00a0on diagnostic \u00a0pitfalls. Jo<\/em>urna<\/em>l of the American Society of <\/em>C<\/em>y<\/em>t<\/em>op<\/em>a<\/em>t<\/em>h<\/em>o<\/em>l<\/em>og<\/em>y<\/em>. 2014;3(4):211\u2013217.<\/p>\n
1<\/strong>4<\/strong>. <\/strong>Odborn\u00e9 usmernenie Ministerstva zdravotn\u00edctva Slovenskej republiky k diagnostike a lie\u010dbe invaz\u00edvnych myk\u00f3z. In: V<\/em>est<\/em>n\u00edk Ministerstva zdravotn\u00edctva Slovenskej <\/em>r<\/em>e<\/em>p<\/em>ub<\/em>li<\/em>k<\/em>y<\/em>. Bratislava, Slovensk\u00e1 republika: V OBZOR, s. r. o.; 2010: 146\u2013159.<\/p>\n
1<\/strong>5<\/strong>. <\/strong>Hoenigl M, Prattes J, Spiess B, et al. Performance of Galactomannan, Beta-D-Glucan, Aspergillus Lateral-Flow Device, Conventional Culture, and PCR Tests with Bronchoalveolar Lavage Fluid for Diagnosis of Invasive Pulmonary Aspergillosis. J Clin Microbiol. <\/em>2014;52(6):2039\u20132045.<\/p>\n
1<\/strong>6<\/strong>. <\/strong>Wheat LJ, Walsh TJ. Diagnosis \u00a0of invasive aspergillosis \u00a0by galactomannan antigenemia detection using an enzyme immunoassay. E<\/em>u<\/em>r <\/em>J Clin Microbiol Infect Dis. <\/em>2008;27(4):245\u2013251.<\/p>\n
1<\/strong>7<\/strong>. <\/strong>Racil Z, Kocmanova I, Lengerova M, et al. Difficulties in using 1,3-\u03b2-D-glucan as the screening test for the early diagnosis of invasive fungal infections in patients with haematological malignancies \u2013 high frequency \u00a0of falsepositive results and their analysis. J Med Microbiol<\/em>. 2010;59(9):1016\u20131022.<\/p>\n","protected":false},"excerpt":{"rendered":"
*All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf\u00a0 attachment at the end of the paper.   V posledn\u00fdch \u00a0rokoch sa roz\u0161iruje spektrum etiologick\u00fdch agensov infekci\u00ed z d\u00f4vodu narastaj\u00faceho po\u010dtu imunokompromitovan\u00fdch jedincov lie\u010den\u00fdch agres\u00edvnymi chemoterapeutikami, a tie\u017e v\u010faka zlep\u0161uj\u00facim sa mo\u017enostiam diagnostiky. Do popredia sa dost\u00e1vaj\u00fa<\/p>\n","protected":false},"author":7,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_mi_skip_tracking":false,"footnotes":""},"categories":[292],"tags":[641,640,637,643,639,642,638,636],"class_list":["post-1038","post","type-post","status-publish","format-standard","hentry","category-microbiology","tag-allergic-bronchopulmonary-aspergillosis","tag-aspergilloma","tag-aspergillus-fumigatus","tag-bronchoalveolar-lavage","tag-chronic-necrotizing-pulmonary-aspergillosis","tag-galactomannan","tag-invasive-pulmonary-aspergillosis","tag-pulmonary-aspergillosis","typ_clanku-review-article"],"acf":{"casopis":[{"ID":991,"post_author":"7","post_date":"2017-02-01 09:43:42","post_date_gmt":"2017-02-01 08:43:42","post_content":"