Significance of interleukin-5, interleukin-17, interleukin-33, periostin and fractional exhaled nitric oxide in a bronchial asthma phenotype evaluation

[A. Plavšić]

98 str.

Medicina - Zapaljenje i autoimunost / Medicine - Inflammation and autoimmunity

Uvod: Astma je sindrom koji karakterišu inflamacija disajnih puteva, raznovrsnost i varijabilnost patofizioloških mehanizama, kliničke prezentacije i odgovora na terapiju. Sastoji se od različitih endotipova i fenotipova, u čijoj evaluaciji i identifikaciji značajnu ulogu imaju indukovani sputum i biomarkeri. Ciljevi istraživanja: Ciljevi ovog istraživanja su odrediti inflamatorne fenotipove u astmi na osnovu analize indukovanog sputuma; ispitati povezanost potencijalnih biomarkera (eozinofili, IgE, periostin, frakcija izdahnutog azot monoksida (FeNO), IL-5, IL-6, IL-17A, IL-33) i inflamatornih fenotipova određenih analizom indukovanog sputuma i ispitati povezanost težine kliničke slike, težine i stepena kontrole astme sa biomarkerima i inflamatornim fenotipovima. Materijal i metode: Sprovedena je studija preseka koja je obuhvatila 80 ispitanika, starijih od 18 godina, sa dijagnozom bronhijalne astme, koji su lečeni na Klinici za alergologiju i imunologiju Univerzitetskog kliničkog centra Srbije. Kriterijumi za isključivanje iz istraživanja su bili primena sistemskih kortikosteroida, prisustvo respiratorne infekcije 4 nedelje pre istraživanja, prisustvo SARS-Cov-2 infekcije 3 meseca pre istraživanja. Svim pacijentima je u istom danu urađeno: detaljna evaluacija kliničkih karakteristika, evaluacija terapije, fizikalni pregled, testovi za procenu kontrole astme, kožne prick probe na standardne inhalacione alergene, FeNO, impulsna oscilometrija, spirometrija, analiza indukovanog sputuma, laboratorijske analize. Za procenu kontrole astme su korišćeni test o kontroli astme (engl. Asthma control test-ACT), upitnik za kontrolu astme (engl. Asthma Control Questionnare-ACQ), GINA (Global Initiative for Asthma) upitnik o kontroli simptoma. U uzorcima perifrene krvi su analizirani kompletna krvna slika sa leukocitarnom formulom, standardne biohemijske analize, C reaktivni protein, IgE, IL-6. Metodom enzimskog imunoeseja (engl. enzyme linked immunoabsorbent test- ELISA) su određivani IL-5, IL-17A, IL-33, periostin, IL-8. Rezultati: Ispitivanjem je obuhvaćeno 80 ispitanika sa bronhijalnom astmom, prosečne starosti 43.65±12.72 godina, dominantno ženskog pola (71.3%), više od polovine su bili pušači ( 56.3%) i prekomerno uhranjeni ( 58.8%). Prosečno trajanje astme je bilo 7 godina, najčešće udružene bolesti su bile alergijski rhinitis (79%), alergije na lekove (27%) i nealergijski rinitis (19%), a u porodičnoj anamnezi najzastupljenije bolesti su bili alergijski rinitis ( 48.8%) i bronhijalna astma (38.8%). Bilošku terapiju je primalo 17 pacijenata, omalizumab 10 pacijenata (58.8%), a benralizumab 7 pacijenata (41.2%). Nekontrolisana astma procenjena GINA upitnikom o kontroli simptoma, ACT i ACQ je utvrđena kod 41%, 36% i 47% ispitanika. Prema ACQ, broj leukocita i limfocita u krvi je bio značajno viši kod loše kontrolisanih pacijenata u poređenju sa dobro kontrolisanim (p=0.009 i p=0.004). Pacijenti sa lošom kontrolom bolesti su imali najviši broj limfocita u krvi shodno ACT (p=0.050)...

Introduction: Asthma is a syndrome that is characterized by airway inflammation, diversity, and variability in pathophysiological mechanisms, clinical presentation, and therapy response. Asthma incorporates different endotypes and phenotypes, where induced sputum and biomarkers have an important part in its determination and evaluation. Aims: The aim of this study was to determine the frequency of different inflammatory phenotypes based on induced sputum analysis, to evaluate the connection between inflammatory phenotypes and biomarkers (eosinophils, IgE, fractional exhaled nitric oxide (FeNO), serum periostin, IL-5, IL-6, IL- 17A, IL-33) and to evaluate the association between asthma control and biomarkers in different asthma phenotypes. Materials and methods: This was a cross-sectional study that included 80 asthma patients, ≥18 years of age, who were examined at the Clinic for Allergy and Immunology, University Clinical Centre of Serbia. The exclusion criteria were the use of systemic corticosteroid therapy, a history of respiratory tract infections in the past 4 weeks, and a documented COVID-19 infection less than 12 weeks before the study. All participants underwent a detailed evaluation of clinical characteristics, personal and family history, triggers of exacerbations, medical asthma history, physical examination, asthma control assessment, skin prick test, FeNO measurement, impulse oscillometry, blood tests, spirometry, induced sputum analysis on the same day, followed in this order. Asthma control was assessed by the Asthma control test (ACT); Asthma Control Questionnaire (ACQ) and GINA (Global Initiative for Asthma) asthma symptom control assessment. The complete blood count, routine blood test, total serum IgE, C-reactive protein (CRP), IL-6 were collected. Serum levels of IL-5, IL-17A, IL -33, IL-8 and periostin were measured using ELISA (enzyme-linked immunosorbent assay). Results: We investigated 80 asthma patients with an average age of 43.65±12.72 years, mostly female (71.3%), more than half were smokers (56.3%) and overweight (58.8%). The median asthma duration was 7 years, the most common comorbidities were allergic rhinitis (79%), drug allergy (27%) and non allergic rhintis (19%), with a family history of allergic rhinitis ( 48.8%) and asthma (38.8%) being the most common. Biological therapy was administered in 17 patients: omalizumab in 10 (58.8%), and benralizumab in 7 (41.2%).Uncontrolled asthma was recorded in 41%, 36% and 47% based on GINA asthma symptom control, ACT i ACQ, respectively. Number of blood leucocytes and lymphocytes was significantly higher in uncontrolled asthma based on ACQ, compared to well-controlled (p=0.009 and p=0.004, respectively). According to ACT, uncontrolled patients had the highest lymphocytes(p=0.050)...

astma, inflamatorni fenotipovi, indukovani sputum, biomarkeri

asthma, inflammatory phenotypes, induced sputum, biomarkers

616-097:616.248(043.3)

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