Have we Made Progress in the Treatment of Asthma?

Astma je složen respiratorni poremećaj koji karakterizira izražena heterogenost u pokretačima bolesti i individualnim reakcijama na terapiju. Identificirano je nekoliko fenotipa astme, svaki definiran jedinstvenom interakcijom između genetskih i okolišnih čimbenika, uključujući upalne, kliničke karakteristike povezane s pokretačem bolesti. Različiti endotipovi astme, temeljeni na upalnom odgovoru, nazvani T2-high (T2) i T2-low astmom, doveli su do razvoja bioloških tretmana usmjerenih na različite upalne medijatore. U T2 astmi vodeće obilježje je povišena razina eozinofila u krvi i sputum, ali i drugih markera kao što su IgE u serumu, frakcija izdahnutoga dušičnog oksida i periostina. U kliničkoj praksi anti-IgE biološka terapija omalizumabom značajno je smanjila egzacerbacije astme. Dva različita humanizirana monoklonska antitijela anti-IL-5 (mepolizumab i reslizumab) te benralizumab (kao anti-IL-5Rα), značajno su smanjila rizik od egzacerbacija i poboljšala plućnu funkciju u usporedbi s placebom. Napredak u razumijevanju mehanizama T2-high (T2) i T2-low astme i biomarkera može pomoći u unapređivanju mogućnosti liječenja za mnoge pacijente s astmom koji ostaju nekontrolirani unatoč korištenju postojeće terapije.Asthma is a complex respiratory disorder characterized by marked heterogeneity in individual patient disease triggers and response to therapy. Several asthma phenotypes have been identified, each defined by a unique interaction between genetic and environmental factors, including inflammatory, clinical and trigger-related characteristics. Different endotypes of asthma, based on the inflammatory pattern, may be regarded as T2-high (T2) or T2-low asthma, have led to the development of biological treatments targeting different inflammatory mediators. The hallmarks of T2 asthma are increased levels of blood and sputum eosinophils and other markers such as serum IgE, fractional exhaled nitric oxide and periostin. In clinical practice, omalizumab, an anti-IgE antibody biologic treatment, significantly reduced asthma exacerbations. Two different anti-IL-5 humanized monoclonal antibodies, mepolizumab, reslizumab and benralizumab as anti-IL-5Rα, significantly reduced the risk of exacerbations and improved lung function compared to placebo. Improving the understanding of T2-high and T2-low mechanisms and biomarkers may help to advance treatment options for many patients with asthma who remain uncontrolled despite the use of current standard of care