The Future of Diagnosis and Treatment of Asthma

Na temelju profi la ekspresije različitih gena na epitelnim stanicama bronha u budućnosti će se moći dijagnosticirati molekularni supfenotipovi astme: a) astma s jakim obilježjima Th2-upale, b) astma sa slabim obilježjima Th2-upale, c) astma bez obilježja Th2-upale. Analizom sveukupne ekspresije gena izdvojena su tri patognomonična IL-13-inducibilna gena u obrisku bronhalnog epitela: periostin, regulator kloridnih kanala 1 (CLCA1) i inhibitor serpin peptidaze B, 2. član (SERPINB2) koji mogu poslužiti kao surogatni biljezi Th2-infl amacije. Gen čija se ekspresija najviše razlikuje u astmi s jakim obilježjima Th2-upale i astmi sa slabim obilježjima Th2-upale jest CCL26 (eotaksin 3). Patofi ziološki mehanizmi preko IL-25, IL-33 i TSLP (engl. thymic stromal lymphopoietin) nalaze se u podlozi astme bez obilježja Th2-upale koja ima slab odgovor na trenutačno dostupnu antiastmatsku terapiju. Najveća je potreba za određivanjem fenotipa bolesti u populaciji bolesnika s teškom astmom te onih s astmom refraktornom na terapiju. Teška astma mogla bi se dokazivati i određivanjem genskog profila alveolarnih makrofaga iz induciranog sputuma. Prediktor porasta FEV1 nakon primjene anti-IL-13-monoklonskog protutijela jest kombinacija serumskog periostina s frakcijom NO u izdahnutom zraku, FeNO. Kombinacija urinarnog leukotrijena E4 s FeNO, tj. njihov omjer, pokazala se kao dobar biomarker kojim se može predvidjeti učinak terapije u astmi. Urinarni bromotirozin može biti marker kontrole astme i prediktor egzacerbacije astme u djece. Liječenje astme u budućnosti temeljit će se na farmakogenetičkim nalazima. U kliničkoj medicini samo je jedan lijek iz skupine bioloških lijekova (monoklonskih protutijela), omalizumab, blokator serumskog IgE, odobren za primjenu u bolesnika s teškom alergijskom astmom.The expression profile of various genes in epithelial cells of the bronchi will enable the diagnosis of molecular subphenotypes of asthma: a) asthma with strong features of Th2 infl ammation, b) asthma with weak features of Th2 infl ammation, and c) asthma without features of Th2 infl ammation. The analysis of the overall gene expression gave three pathognomonic genes, i.e. IL-13 inducible genes in bronchial epithelial swab: periostin, chloride channel regulator 1 (CLCA1) and serpin peptidase inhibitor, clade B (SERPINB2), which may serve as surrogate markers of Th2 inflammation. The gene whose expression diff ers most in asthma with strong features of Th2 infl ammation and asthma with weak features of Th2 infl ammation is CCL26 (eotaxin-3). Pathophysiological mechanisms, which act via IL-25, IL-33 and TSLP (thymic stromal lymphopoietin), underlie asthma without features of Th2 infl ammation and a weak response to the currently available antiasthmatic therapy. The need to identify a phenotype of the disease is the greatest in patients with severe asthma and those with asthma refractory to therapy. Severe asthma could be also diagnosed by determining the genetic profi le of alveolar macrophages from induced sputum. The predictor of FEV1 growth after the administration of anti-IL-13 monoclonal antibody is a combination of serum periostin with NO fraction in exhaled air (FeNO). The combination of urinary leukotriene E4 with FeNO, i.e. their ratio, proved to be a good biomarker of therapy efficiency in asthma. Urinary bromotyrosine could be a marker of asthma control and a predictor of asthma exacerbations in children. In the future, the treatment of asthma will be based on pharmacogenetic findings. In clinical medicine, there is only one biosimilar drug, i.e. omalizumab (monoclonal antibody, serum IgE blocker), authorised for use in patients with severe allergic asthma