Introduction. Guidelines on Biological Therapy for Bronchial Asthma of the European Academy of Allergy and Clinical Immunology (EAACI) identified a number of controversial issues for additional outcome analysis using randomized clinical trials and data from routine clinical practice. In particular, there is unmet need to clarify algorithms for prescribing biologicals using predictors of response and its timing, taking into account risk factors and multimorbidity. Omalizumab is a recombinant humanized monoclonal anti-IgE antibody of IgG1 class used for the treatment of severe refractory atopic bronchial asthma (BA) and a variety of IgE-mediated diseases. Among biological agents, this "pioneer molecule" has the greatest experience in the "allergology and immunology" profile. Detailed description of the "nonresponders" portraits will allow to perform the therapy response assessment on time and facilitate rational planning of individual therapy, which is a prerequisite for biologicals era. Using only routine methods, it is possible to perform initial and dynamic screening to phenotype a heterogeneous cohort of patients with severe asthma and chose the optimal strategy. Aim. To identify predictors of nonresponse to omalizumab anti-IgE therapy in patients with severe atopic BA and to establish optimal timing of efficacy assessment using retrospective analysis of data from the Biologic Therapy Registry of Allergology and Immunology in routine clinical practice. Materials and methods. A retrospective single-center registry study was conducted at the Allergy and Immunology Reference Center from June 2017 to August 2021. 135 patients with severe BA, with confirmed perennial sensitization, who received omalizumab according to the recommendations of the current version of GINA, were selected from the clinical and dynamic observational system (registry). Dosing regimen and administration frequency of omalizumab were determined in accordance with the instructions for the drug. Assessment of therapy efficacy was performed at the time point 4, 6 and 12 months. Patients were subgrouped into "responders" and "non-responders" according to the following criteria: ACT score less than 19 and/or difference between initial ACT score in dynamics less than 3 points; forced expiratory volume in the first second less than 80%; combination of these two criteria. Nonparametric methods of descriptive statistics were used in data processing: median, interquartile range. Differences were considered significant at p0.05. MannWhitney U-test, KruskalWallis one-way analysis of variance, and Fisher's 2 test were used to compare quantitative characteristics. Results. Heterogeneous subgroups of patients differing in reaching the criteria of "non-responders" to treatment were identified; the informativity of modifiable and unmodifiable factors differed at time-points of dynamic observation. In the differential analysis, two profiles of "nonresponders" were defined in combination with the most significant predictors of "nonrsponse" to omalizumab. According to the data obtained, one of the clinical phenotypes, namely the combination of severe asthma with the Samters triad, corresponded to the characteristics of the patient "nonresponders": age of onset is about 30 years, females, severe exacerbations of BA while taking non-steroidal anti-inflammatory drugs, accompanied with high levels of eosinophilia. Conclusion. The data obtained illustrates the hypothesis of pathogenetic heterogeneity of severe BA with the phenomenon of overlapping phenotypes and can serve as an additional orienteer for creating the individual plan of anti-IgE therapy in real clinical practice.
Common variable immune deficiency is the most common form of a group of primary immunodeficiencies in adult patients. Pulmonary complications occupy leading positions. It is the development of recurrent bronchopulmonary inflammatory diseases that is considered to be one of the main causes of death and disability in patients with this disease. By presenting two clinical cases with long diagnostic delays, the authors try to attract the attention of specialists of related professions, which will minimize the development of irreversible complications in the patients.
Журнал для непрерывного медицинского образования врачей COVID-19 у больных, получающих лечение программным гемодиализом ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ 1 Государственное бюджетное учреждение здравоохранения города Москвы «Городская клиническая больница № 52 Департамента здравоохранения города Москвы», 123182, г. Москва, Российская Федерация 2 Федеральное бюджетное учреждение науки «Московский научноисследовательский институт эпидемиологии и микробиологии им. Г.Н. Габричевского» Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человека, 125212, г. Москва, Российская Федерация 3 Филиал федерального государственного бюджетного военного образовательного учреждения высшего образования «Военно-медицинская академия имени С.М. Кирова» Министерства обороны Российской Федерации, 107392, г. Москва, Российская Федерация 4 Федеральное государственное бюджетное образовательное учреждение высшего образования «Московский государственный медикостоматологический университет имени А.И. Евдокимова» Министерства здравоохранения Российской Федерации, 127473, г. Москва, Российская Федерация 5 Федеральное государственное бюджетное учреждение «Главный военный клинический госпиталь им. Н.Н. Бурденко» Министерства обороны Российской Федерации, 105229, г. Москва, Российская Федерация
Background. Fungal sensitization (FS) often escapes the attention of clinicians when assessing the spectrum of sensitization in patients with atopic diseases. According to cohort studies is found in 310% of the general population and in 720% of asthmatics; the proportion of patients with severe bronchial asthma (SBA) with HS ranges from 35 to 75%. Fungal conidia have a 1000-fold higher exposure and are among the most important clinically relevant allergens in asthma. Exposure to fungal allergens is capable of generating a sustained T2 response with production of proinflammatory cytokines such as IL-5 and 13, which is indirectly related to the severity of airway eosinophilia. The identification of specific serum IgE is considered the benchmark diagnostic sign of FS, and the encapsulated hydrophobic carrier polymer system is considered preferable to skin prick tests. The process of reclassifying diseases with fungal lung lesions is confusing treatment strategies, leaving the FS problem underestimated. A series of publications have shown that omalizumab and other biologics targeting IL-5 or IL-5 receptor (IL5R) alpha are effective in treating SBA with FS. However, there remains an unmet need in real clinical practice for standardized approaches to genetically engineered biological therapies (BT) for different phenotypes of SBA, especially those associated with impaired microbiological homeostasis and this type of sensitization. Aim. Using retrospective analysis of clinical-dynamic observational data from patients on BT treatment in a real clinical setting to determine phenotypic features of severe allergic bronchial asthma with FS and to perform additional detailed analysis of a cohort of patients on anti-IgE therapy. Materials and methods. A retrospective observational single-center registry study was conducted between June 2017 and August 2021 at the City Reference Center for Allergology and Immunology. The baseline cohort consisted of 198 patients with severe allergic AD who were in the initial phase of BT. Inclusion criteria: age of patients over 18 years; presence of severe allergic bronchial asthma. Complex initial examination of patients included determination of FS by two methods: ImmunoCap ISAC to fungal allergic components alt a1, alt 6 (fungi of genus Alternaria) and asp f1, asp f3, asp f6 (fungi of genus Aspergillus). Specific IgE determinations on fungal panels. Sensitization to fungi was detected in 47 people during allergy examination. The following criteria were considered in evaluation of response to omalizumab: AST score less than 19 and/or difference between initial AST score and this score in dynamics less than 3 points; FEV 1 score less than 80; combination of 2 listed criteria. The minimum period of BT was 16 weeks. Nonparametric methods of descriptive statistics were used: median, interquartile range. Differences were considered significant at p0.05. Data were statistically processed using nonparametric methods in IBM SPSS Statistics V-22 program. MannWhitney U-test and KruskalWallis one-way analysis of variance were used to compare quantitative characteristics. Fisher's 2 test was used to compare qualitative characteristics. Results. Characteristics of the eosinophilic phenotype of SBA combined with FS: middle-aged patients, more often women, with relatively early onset of AD and high baseline eosinophil levels before prescription of biological drug therapy. Concomitant atopic dermatitis and food allergies are additional frequent features of this phenotype. Analysis of the effect of FS on achieving response to omalizumab and further consideration of switching to alternative therapy in SBA and FS patients showed the need to avoid premature revision and perform no earlier than the 10th month of therapy due to delayed response formation. Given the aggressive impact of FS on the barrier functions of the bronchial tree epithelium, it is advisable to test patients for FS at the initial diagnosis of AD. In the presence of atopic dermatitis and/or food allergy as T2 comorbidities in patients with SBA, early testing for FS and increased control of local and systemic inflammation are appropriate, which may improve long-term outcomes and reduce risks of further damage to natural barriers. Conclusion. Further research on various aspects of FS and its role in allergic diseases is extremely relevant in the current context.
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