Биомаркеры воспаления дыхательных путей у пациентов с тяжелой бронхиальной астмой в реальной клинической практике

Severe asthma is a heterogeneous disease consisting of several endotypes and phenotypes diagnosed due to different biomarkers. Frequency of different endotypes and phenotypes in real clinical practice needs further investigation.The aim of this study was to assess biomarkers of T2-inflammation in patients with severe asthma in a single secondary care center.Methods. We examined 96 adult outpatients (34% male) with severe asthma. Data collected included demographics, smoking history, asthma exacerbations during previous 12 months, medication use, comorbidities. Lung function tests were assessed by using the Spirograph 2120 (Vitalograph, Great Britain). Blood eosinophils (Eos) were measured by automatic haemoanalyser. Atopic status was determined by positive skin prick-test (> 3 mm) and/or serum specific IgE to common inhalant allergens. Serum total IgE levels were assessed by immunofluorescence assay. FeNO was measured by a chemiluminescence analyzer (Model LR4000; Logan Research, Rochester, UK). Presence of allergy, need for regular oral steroid use, blood Eos ≥ 150 cell/μl and FeNO ≥ 20 ppb were considered as markers of T2-driven inflammation. Asthma control and quality of life were assessed by using Russian versions of ACQ-5 and St. George's Respiratory Questionnaire (SGRQ). Statistical analyses were performed with Statistica Ver. 10.0 (StatSoft, Inc., USA).Results. The majority of patients with severe asthma (93%) have at least one or more elevated markers (presence of allergy, need for regular oral steroid use, Eos ≥ 150 cell/μl or FeNO ≥ 20 ppb) of T2-inflammation. Biomarkers levels did not differ in non-steroid-dependent and steroid-dependent patients. The most frequent markers were allergy and blood Eos ≥ 150 cell/μl. Two or more elevated biomarkers were revealed in 72% of patients.Conclusion. The majority of patients with severe asthma in real clinical practice have signs of T2-inflammation. It seems that many severe asthmatics have indications for prescription of biological and can be treated by more than one of monoclonal antibodies against major cytokines of T2-inflammation.Тяжелая бронхиальная астма (БА) является гетерогенным заболеванием, представленным разными фенотипами и эндотипами, для диагностики которых используются различные биомаркеры. Частота фенотипов и эндотипов тяжелой БА в реальной клинической практике изучена недостаточно.Целью исследования явилась оценка биомаркеров Т2-воспаления дыхательных путей у пациентов с тяжелой БА.Материалы и методы. Обследованы взрослые амбулаторные пациенты (n = 96; 34 % – мужчины; возраст – 18–78 лет) с тяжелой БА. Исследование функции легких выполнялось методом спирометрии (спирограф 2120, Vitalograph, Великобритания) с оценкой обратимости обструкции. Оценка чувствительности к основным ингаляционным аллергенам осуществлялась с помощью кожных проб и / или уровней специфического иммуноглобулина (Ig) E в сыворотке крови. Содержание эозинофилов в периферической крови определялось импедансным методом на автоматическом гемоанализаторе. Уровень оксида азота выдыхаемого воздуха (FeNO) измерялся при помощи хемилюминисцентного газоанализатора (Logan 4100, Великобритания), уровень общего IgE сыворотки крови определялся методом иммунофлюоресцентного анализа. Контроль над БА и качество жизни пациентов оценивались при помощи русскоязычных версий Опросника по контролю над БА (Asthma Control Questionnaire – ACQ-5) и респираторного вопросника Госпиталя Святого Георгия (St. George's Respiratory Questionnaire – SGRQ). Статистический анализ проводился с использованием параметрических и не - параметрических методов пакета прикладных программ Statistica 10.Результаты. У подавляющего большинства (93 %) пациентов с тя - желой БА выявлен хотя бы один из критериев Т2-воспаления дыхательных путей (уровень эозинофилов ≥ 150 кл. / мкл и / или FeNO ≥ 20 ppb, клинически значимая гиперчувствительность к аллергенам или потребность в регулярной терапии системными глюкокортикостероидами. Уровни биомаркеров значимо не различались при наличии гормональной зависимости и ее отсутствии. Среди маркеров наиболее часто отмечались аллергия и уровень эозинофилов ≥ 150 кл / мкл. У 72 % больных выявлено одновременное повышение уровня нескольких биомаркеров.Заключение. В большинстве случаев тяжелой БА в реальной клинической практике отмечается Т2-эндотип заболевания, при выявлении которого назначается биологическая терапия. Более чем у половины больных установлен перекрест показаний для назначения разных препаратов моноклональных антител к основным цитокинам Т2-воспаления

Diagnosis and treatment of hereditary angioedema with normal C1-inhibitor level

Hereditary angioedema (HAE) with normal C1-inhibitor level is a rare potentially life-threatening disorder with autosomal dominant inheritance which was first described in 2000. Its clinical presentation is similar to HAE with C1-deficiency. The review is summarized data about its prevalence, mechanisms, genetics and diagnostic criteria. Different subtypes and treatment options (on demand, short term and long-term prophylaxis) are discussed. We describe family clinical cases of 2 female patients with normal C1-inhibitor and plasminogen gene mutation. Their features were late diagnosis (in 10 and 25 years after the onset of symptoms), family history (similar genetic mutation in 3 female members of the same family, including 1-asymtomatic) and combination of face, tongue, larynx and abdominal angioedema in patient and her sibling

Bronchial asthma. Alone with the doctor

Sound approach to patient management is based on the evaluation of the overall clinical and functional pattern of the disease, including RF changes and other parameters. According to its concept, personalized treatment should be regarded as a specific creative process based on international guidelines and achievements of the modern healthcare

Mild bronchial asthma: a modern treatment concept

Mild bronchial asthma (BA) occurs in 50–75% of patients with this disease. It is characterized by clinical symptoms that are controlled by low doses of inhaled glucocorticoids (IGCS) or anti-leukotriene drugs. Mild BA reduces the quality of life of patients, is accompanied by the development of severe, in some cases fatal exacerbations, and is characterized by a significant cost of treatment. One of the main problems in the management of patients with this disease is their low adherence to IGCS treatment and the excessive use of short-acting 2-adrenomimetic agents. Several clinical studies have shown that the use of a combination of budesonide/formoterol (Symbicort® Turbuhaler®) in an «as needed» mode reduces the incidence of severe exacerbations of mild BA as well as low doses of budesonide, and is characterized by a lower cumulative dose of this glucocorticoid. The results obtained were the basis for the creation of a new treatment concept, which gives preference to the combination of IGCS / formoterol «as needed» in mild BA as a supporting therapy, and for the management of symptoms of the disease

Clinical profile of patients with severe asthma

The article presents the results of the authors' trial involving 119 patients (aged 22 to 82 years) with severe bronchial asthma (BA) diagnosed according to the ERS/ATS guidelines (2014). Allergic asthma was diagnosed in 77% of patients. The study focused on house dust mites as the main allergens in the sensitization spectrum. A significant proportion of patients (82%) had uncontrolled course of the disease, and 76% suffered from airflow limitation that is not fully reversible. Markers of eosinophilic airway inflammation (nitric oxide in exhaled air and level of blood eosinophils above 150 cells per 1 µL) were found in 63% of patients. Good adherence to treatment (administration of more than 75% of the prescribed doses of drugs) was observed in 61% of patients. Among patients with severe asthma 27% were active smokers. Smokers demonstrated a decreased pulmonary function and a lower level of nitric oxide in exhaled air. Smokers were also less adherent to treatment with inhaled corticosteroids. Severe BA was combined with COPD in 37% of cases