The research of bronchial remodeling and the role of angiogenesis processes in it are currently relevant for the study of the phenotypic features of the course of bronchial asthma in children and require further study in order to develop preventive and therapeutic measures. Purpose - to optimize treatment and prevention measures for persistent bronchial asthma (pBA) in children, to determine the clinical and anamnestic features of its phenotype, taking into account the accumulation of mediators of neoangiogenesis (фактора росту ендотелію судин - VEGF, матрична металопротеїназа-9 - MMP-9) in the respiratory tract as markers of bronchial remodeling. Materials and methods. A comprehensive examination of 116 children with pBA aged from 6 to 17 years (average age 11.6±0.29 years) and disease duration of 4.9±0.38 years was conducted. Three clinical groups were formed: the Group 1 was formed by 37 children with pBA with VEGF >80.0 ng/ml and MMP-9 >5.2 ng/ml in the sputum supernatant; the Group 2 included 41 children with an excess of one of these markers; and the control group consisted of 38 patients with values of these biomarkers below the median (VEGF<80.0 ng/ml and MMP-9 <5.2 ng/ml). The main clinical characteristics of the observation groups were comparable. Results. The article shows that uncontrolled pBA (sum of points >20) during the 4-year follow-up occurred most often in children of еру Group 1 and the Group 2, and indications of insufficient control of asthma indicated a probable risk of developing structural changes in the bronchi: OR - 2.23 (95% CI: 1.2-4.1), RR - 1.5 (95% CI: 1.0-2.2) and RR - 22%. The severe course of pBA was also associated with the risk of bronchial remodeling with the accumulation of angiogenesis mediators in their lumen as follows: OR - 2.2 (95% CI: 1.1-4.52), RR - 1.42 (95% CI: 1.0-2.5) and AR - 19%. Accumulation of remodeling markers in airways in patients with asthma in the Group 1 and the Group 2 is associated with a predominantly eosinophilic phenotype of the disease. At the same time, patients with a low content of markers of bronchial remodeling in sputum (control group) have better chances of achieving complete control over the symptoms of pBA compared to children with a high content (total absolute risk - 19.0%, total relative risk - 45.1%, the minimum number of patients who need to be treated to obtain a positive result - 2.2) and average (total absolute risk - 10.2%, total relative risk - 30.6%, the minimum number of patients who need to be treated to obtain a positive result - 3.2) content of angiogenesis factors in sputum. Conclusions. In patients with pBA, the accumulation of markers of bronchial remodeling in the lumen of the airways was associated with a severe uncontrolled course of asthma and worse chances of achieving disease control. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.
Background. Objective: to study the diagnostic value and indicators of clinical and epidemiological risk of some immunological biomarkers as indicators of the severity of the clinical course of neonatal sepsis in order to improve treatment outcomes in newborns with neonatal sepsis with an alternative serum content of C-reactive protein. Materials and methods. A comprehensive clinical and paraclinical examination of 56 children with neonatal sepsis was conducted. The severity of neonatal sepsis was determined using the constellation-diagnostic scales of multiple organ dysfunction such as SNAPII, SNAPРЕII, PELOD, SOFA, nSOFA, PEMOD, SCRIB, NEOMOD. The comprehensive immunological examination with evaluation of immunoglobulin A, G, M, C-reactive protein, presepsin, procalcitonin, interleukins (IL) 6, 8, 10 content in blood serum was conducted in all newborns. Two clinical groups were formed. The clinical group I included 25 infants with neonatal sepsis with a serum level of C-reactive protein < 20 mg/l (boys — 52.0 %, city residents — 80.0 %, the average content of C-reactive protein — 8.80 ± 0.41 mg/l). The clinical group II was formed by 31 children with neonatal sepsis and C-reactive protein blood concentration > 20 mg/l (with 62.8 % of boys, p > 0.05; 57.1 % of city residents, p > 0.05; the average content of C-reactive protein — 29.70 ± 1.89 mg/l, р < 0.05). According to the main clinical characteristics, the observation groups were comparable. Results. The conducted studies showed that the severity of the clinical course of neonatal sepsis, determined using the constellation-diagnostic scales of multiple organ dysfunction (SNAPII, SNAPРЕII, PELOD, SOFA, nSOFA, PEMOD, SCRIB, NEOMOD), did not reveal any significant differences in the comparison groups. It was found that in newborns with a C-reactive protein content < 20 mg/l, compared to representatives of the clinical group II, the concentration of IL-6, IL-8 and IL-10 was lower by 1.7, 1.5 and 1.8 times, respectively. Thus, patients of the group II had the risk of increasing serum content of IL-6 > 31.4 pg/ml (relative risk (RR) 1.7 (95% confidence interval (CI): 1.3–2.2) with an odds ratio (OR) 2.8 (95% CI: 1.6–5.1)), IL-10 > 18 pg/ml (RR 1.7 (95% CI: 1.1–2.4) with an OR 2.9 (95% CI: 1.6–5.3)), and IL-8 > 24.0 pg/ml (RR 1.9 (95% CI: 1.2–3.1) with an OR 4.7 (95% CI: 2.5–8.8)). Among the studied immunological biomarkers, the concentration of presepsin > 1,000 ng/ml was accompanied by the best indicators of the clinical and epidemiological risk of severe sepsis according to the constellation-diagnostic scales of multiple organ dysfunction (odds ratio 4.3–6.0, relative risk 2.3–2.5, attributable risk 32.0–42.0 %). Conclusions. Elevated content of some markers of neonatal sepsis (presepsin, procalcitonin) and interleukins (IL-6, IL-8) can be considered a biomarker of a severe course of neonatal sepsis with probable development of multiple organ dysfunction.
Diagnosis of acute infectious-inflammatory processes of the lower respiratory tract with a respect to justify etiotropic therapy is often based on evaluation of the activity of blood inflammatory markers and data of lungs' X-ray examination, but scientific evidence of their informativity in the differential diagnosis of community-acquired pneumonia and acute bronchitis is conflicting. Purpose — to study the predictor role of some paraclinical indices in the verification of infectious and inflammatory diseases of the lower respiratory tract (community-acquired pneumonia and acute obstructive bronchitis) in children of different ages in order to optimize the treatment. Materials and methods. To achieve the goal of the study, a cohort of patients with acute infectious-inflammatory pathology of children with different ages (75 patients) who received inpatient treatment at the pulmonology department of the Regional Children's Clinical Hospital in Chernivtsi has been formed by the method of simple random sampling. The first (I) clinical group was formed by 51 patients with a verified diagnosis of community-acquired pneumonia (CAP), acute course, and the second (II) clinical group included 24 children, in which the infiltrative acute process in the lungs was excluded, but who had broncho-obstructive syndrome. According to the main clinical characteristics, the comparison groups have been comparable. The results of the study have been analyzed by parametric («P», Student's criterion) and non-parametric («Рϕ», Fisher's angular transform method) calculation methods, and methods of clinical epidemiology with an evaluation of the diagnostic value of the tests has been performed taking into account their sensitivity (Se) and specificity (Sp), as well as attributive (AR) and relative (RR) risks, and the odd ratio (OR) of the event, taking into account their 95% confidence intervals (95% CI). Results. The analysis of the obtained dada has showed that in the patients with CAP such common inflammatory blood markers (leukocytosis, relative neutrophilosis, shift of leukocyte formula to the left, elevation of erythrocyte sedimentation rate (ESR) or high level of CRP — С-reactive protein) are characterized by low sensitivity (Se in range between 11% and 63%) indicating that they are inadvisable for use as the screening tests for the verification of pneumonia. At the same time, it has been shown that these inflammatory blood markers are characterized by sufficient specificity (in the range from 75% to 93%) in the verification of pneumonia only under their significant increase (total leukocyte count >15.0x109, ESR>10 mm/h and CRP level in blood >6 mg/ml), indicating that they are enough, but only for confirming inflammation of the lung parenchyma. From the standpoint of clinical epidemiology, it has been proved that the asymmetry of findings at lung radiographs (asymmetry of pulmonary enhancement, asymmetric changes of lung roots and, especially, the presence of infiltrative changes at lung parenchyma) are the most informative diagnostic tests in pneumonia verification (ST=90–95%) and have a statistically significant predictor role in the final diagnosis (OR=11.6–150). When assessing the hemogram in children of the II clinical group it has been found that only the relative number of band neutrophils <5%, as a diagnostic test, had an insignificant amount (16%) of false-positive results, which allows to use this marker in confirming the diagnosis of acute obstructive bronchitis, but not as its predictor (OR=2.21; 95% CI: 0.69–7.06) or screening test (Se=29%). At the same time, a significant diagnostic and predictor role of the chest X-ray examination in the differential diagnosis of acute BOS with pneumonia has been established. Namely, symmetrical alteration of the lung root architecture at chest radiographs in the absence of infiltrative changes in the pulmonary fields was characterized by few false-negative results (10%), which allow the use of this feature as a screening pattern in the diagnosis of acute obstructive bronchitis. The absence of changes of pulmonary at chest radiographs should be used to confirm the diagnosis of acute obstructive bronchitis (Sp=98%), but not as a screening sign due to the significant number of negative results in the presence of the disease (Se=48%). Conclusions. In general, the low diagnostic and predicting role of the common blood inflammatory markers for the diagnosis of acute inflammation of the lung parenchyma in children of different ages, as well as in the differential diagnosis of pneumonia and acute obstructive bronchitis have been confirmed. At the same time, it has been found that such radiological features as asymmetry of pulmonary pattern enhancement and the presence of asymmetric infiltrative changes of the lung parenchyma are the most informative diagnostic tests in the verification of pneumonia (Se=80–88% and Sp=90–95%), and have a statistically significant predictor role in the final diagnosis (OR=38.95–150). It has been shown that symmetrical changes of lung roots (their deformation, widening or infiltration) at chest radiographs in the absence of infiltrations in the pulmonary fields, as well as the absence of changes in the pulmonary pattern, have a statistically significant predictor role in the diagnosis of acute obstructive bronchitis (OR=20,78–55,0). The study was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the institution specified in the work. Informed consent was obtained from the parents of the children for the research. The authors declare no conflicts of interest. Key words: community-acquired pneumonia, obstructive bronchitis, children, diagnostic value, predictors.
Вищий державний навчальний заклад України «Буковинський державний медичний університет», м. Чернівці Резюме. Проведення комплексного клінічнопараклінічного обстеження 120 дітей, хворих на бронхіальну астму, дозволило встановити, що найвиразніші показники неспецифічної реактивності бронхів на непрямі бронхоспазмогенні стимули асоціювали з гіпергранулоцитарним запальним патерном крові, за якого зростали шанси підвищеної лабільності дихальних шляхів (показника лабільності бронхів >30 %) у 14,2 раза. Нейтрофільний запальний патерн переважно супроводжувався процесами бронхоконстрикції: шанси наявно-сті показника індексу бронхоспазму >20 % зростали від 3 до 21,3 раза. У кожного п'ятого пацієнта з еозинофільним запальним патерном крові траплялися ознаки значної індукованої обструкції бронхів, а гіпогранулоцитарний запальний патерн асоціював із найнижчими показниками неспецифічної реактивності бронхів. Ключові слова: бронхіальна астма, діти, запальний патерн крові, лабільність бронхів.
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