Analysis of association between histamine receptor gene HRH1, HRH2, HRH3, HRH4 polymorphisms and asthma in children

Asthma is a common multifactorial disease characterized by chronic inflammation of the respiratory tract. Insufficient control of asthma symptoms significantly reduces the patient’s quality of life, leads to the risk for more severe disease and disability. It is important to research the role of gene polymorphisms encoding proteins involved in various stages of histamine metabolism, which is one of the known mediators of allergic reactions.The aim of the study was to investigate histamine receptor gene polymorphisms (HRH1, HRH2, HRH3, HRH4) in children with asthma and the control group.Methods. The study of HRH1 (rs901865), HRH2 (rs2067474), HRH3 (rs3787429), HRH4 (rs11665084) gene polymorphisms in asthma patients and healthy individuals aged 2 - 17 years of different ethnicities living in the Republic of Bashkortostan was carried out. Genotyping of polymorphisms was performed by polymerase chain reaction with fluorescence detection.Results. In Tatars, rs901865*CT genotype and rs901865*T allele of HRH1 gene were associated with asthma development and decrease in spirometry measures (MEF25). In Tatars, a statistically significant model of the interaction between HRH1 (rs901865), HRH3 (rs3787429), and HRH4 (rs11665084) gene polymorphisms that leads to the risk of asthma was established.Conclusion. The results of this study reveal certain aspects of asthma pathogenesis and suggest the possible involvement of polymorphic variants of histamine receptors genes HRH1, HRH3, HRH4 in the development of asthma.

Neuropeptide Y as a potential biomarker in patients with asthma and obesity

The phenotype of asthma with obesity is particularly difficult to treat, while its prevalence is increasing. In recent years, special attention has been paid to neuropeptide Y (NPY) due to its possible effect on the severity of the clinical course of asthma.Aim. To identify the relationship between the level of NPY and the clinical course of asthma in patients with obesity and overweight.Methods. The study included 113 patients (27, or 23.89% of men and 86, or 76.11% of women) diagnosed with asthma of moderate severity, whose average age was 57.81 ± 13.05 years. Patients were divided into three groups — with normal body weight, overweight, and obesity. The examination included spirometry, body mass index (BMI), and a questionnaire. Also, Asthma Control Test (ACT) was used. The levels of leptin, adiponectin, NPY, and general oxidative damage were measured in all patients.Results. Asthma control was significantly lower in the group of patients with asthma and obesity compared with the normal body weight and overweight patients. Leptin level was significantly higher in the group of patients with asthma and obesity compared with the normal body weight and overweight patients. The level of NPY was significantly higher in the group of patients with obesity than in the patients with normal body weight and overweight. No significant differences in the level of adiponectin were found between the groups. The NPY level had a high inverse correlation with VLC index, a moderate/medium inverse correlation with forced expiratory volume in 1 sec, forced expiratory flow (FEF) at 25%; forced vital capacity, Tiffno index, FEF 50%, peak expiratory flow, ACT score, and a moderate positive correlation with the level of total oxidative damage.Conclusion. A higher level of NPY is observed in patients with asthma and obesity. This level has an inverse correlation with spirometric parameters, asthma control (evaluated via ACT) and a positive correlation with the level of general oxidative damage, which indicates a possible proinflammatory effect of NPY that contributes to an unfavorable course of asthma. Thus, further studies are required to establish the nature of the relationship between NPY and asthma exacerbations, as well as the mechanism of NPY influence on asthma pathogenesis.

The clinical significance of the parameters of the capillary bed, heart rate variability, and computer bronchophonography in the differential diagnosis of diseases accompanied by prolonged cough in children

Differentia! diagnosis of the causes of prolonged cough is difficult because of its multifactorial nature. Diagnostics in case of a cough that persists for more than 4 weeks is based on clinical data, but sometimes it is not enough to establish a diagnosis. This issue led to the development of algorithms based on additional diagnostic criteria evaluated with modern non-invasive functional methods for diagnosing diseases accompanied by a prolonged cough in children.Aim. To determine the differential diagnostic value of the functional parameters of the capillary bed, respiratory tract, and autonomic nervous system in children with diseases accompanied by a prolonged cough (more than 4 weeks).Methods. 238 children aged from 2 to 17 years with prolonged cough were examined in inpatient or outpatient settings and divided into 4 groups: Group 1 (n = 68) - patients with acute or exacerbation of the chronic infectious upper respiratory tract diseases; Group 2 (n = 53) - patients with lower respiratory tract infection; Group 3 (n = 39) - patients with allergic rhinitis; Group 4 (n = 78) - patients with bronchial asthma. All patients underwent standard clinical examination. The diagnostic test also included functional assessment of microcirculation, autonomic nervous system, and respiratory system via computer capillaroscopy of the nail bed, evaluation of heart rate variability, and computer bronchophonography.Results. Patients with allergic diseases of the respiratory tract, especially with asthma, show a change in all parts of the capillary bed and a significant increase in the zone of perivascular edema in combination with parasympathicotonia, in contrast to children with infectious diseases of the respiratory system, who showed a change in microcirculation parameters mainly in the venous capillaries in combination with sympathicotonia. In addition, children with prolonged coughing, regardless of its origin, showed functional changes in the high-frequency acoustic parameters of the respiratory system in the form of an increase in the coefficient of the high-frequency acoustic component of breathing (ф3), which indicates bronchial hyperreactivity.Conclusion. The functional parameters of the microvasculature, autonomic nervous system, and respiratory tract can be used as additional differential diagnostic criteria and included in algorithms for diagnosing respiratory diseases of various origins in childhood, contributing to the early detection of the pathology and timely targeted therapy.

Granulomatous lymphocytic interstitial lung disease as a complication of common variable immunodeficiency

Common variable immunodeficiency (CVID) is a rare immunodeficiency, the classic manifestation being recurrent infections. Other lesions are often found in CVID patients, such as malignant neoplasms, autoimmune conditions caused by abnormal cellular immunity, in addition to infectious complications. Usually, the pathological process involves the lungs. This article presents a clinical case of a patient with CVID complicated by granulomatous lymphocytic interstitial lung disease.

Respiratory pathophysiology in obesity

In the modern world, obesity is the most important medical and social problem that requires an interdisciplinary approach. Many diseases of the respiratory system are caused by obesity.Aim. The review analyzes scientific sources on respiratory disorders in patients with obesity from the open-access electronic libraries PubMed and eLibrary published in the last 15 years.Methods. A comparative systematical assessment of the results of these studies was carried out. The mechanical effects of excess body weight on the respiratory apparatus have been singled out. The current views about cellular and humoral effects of adipose tissue on the development of respiratory pathology have been given.Conclusion. The analysis results present evidence of the multifactorial negative influence of excessive body weight on the respiratory system. Some aspects of the role of obesity in the development of respiratory disorders require further study. Understanding the pathogenic mechanisms behind the influence of obesity on the respiratory apparatus is essential for developing the patient management strategy.

The achievements of pulmonology and the main directions of further improvement of medical care in the Russian Federation

The development of pulmonology in Russia is linked with the creative activity of the Scientific Research Institute of Pulmonology of the Federal Medico-Biological Agency (Research Institute of Pulmonology of the FMBA) and its scientific school.The aim of the analytical review was to assess the role and contribution of the research team of the Research Institute of Pulmonology in improving the quality of medical care to the population of Russia.Methods. The data of medical statistics of the Ministry of Health of the Russian Federation on morbidity and mortality of the population due to respiratory diseases (RD) from 2004 - 2018 are analyzed. The publications on scientific research conducted with the participation of employees of the Research Institute of Pulmonology for the period from 2005 to 2020 were studied.Results. Over the past 30 years in Russia, with the participation of the staff of the Research Institute of Pulmonology, the state task of creating a system for organizing medical care for the population with RD has been successfully solved. The study and implementation of modern innovative approaches in the diagnosis, treatment and prevention of RD, the training of primary care physicians allowed to improve the quality of medical care to patients to the level of world standards. For the period from 2004 - 2018 the mortality of the population from RD 35.6% decrease was registered. During the pandemic of a new coronavirus infection, the use of pulmonology achievements in clinical practice contributed to a decrease in the frequency of deaths in people with COVID-19.Conclusion. Currently, the Research Institute of Pulmonology of the FMBA of Russia retains a leading position in the country in the field of fundamental scientific research, innovative methods of diagnosis and treatment of RD, educational activities and training of specialists in the field of pulmonology.

Obstructive sleep apnea syndrome: association of serum melatonin, increased daytime sleepiness, and intermitting night hypoxemia

The relevance of studies related to the features of respiratory disorders during sleep is undeniable due to the steady growth of the worldwide prevalence of apnea syndrome, which leads to a decrease in quality of life, the risk of early cardiovascular diseases together with cerebrovascular, endocrine, and pulmonary disorders.The aim of this study was to determine the relationship between the morning serum melatonin, blood oxygen saturation (SрO2), and increased daytime sleepiness in patients with SOAS, as well as to assess changes in the production of endogenous melatonin after eliminating clinical manifestations of nocturnal hypoxemia, through a 3-month course of non-invasive continuous positive airway pressure (CPAP) therapy. The study enrolled 30 male patients who came to the Federal State Public Scientific Institution “Scientific Centre of Family Health and Human Reproduction Problems” because of snoring, sleep apnea, and increased daytime sleepiness.Methods. Polysomnography, questionnaire, HPLC-MS/MS analysis of serum melatonin levels, CPAP-therapy for the respiratory support at home for 3 months, monitoring of the sleep scores, serum melatonin, and daytime sleepiness after the treatment.Results. A comparative assessment of the sleep scores before and after the respiratory support for 3 months revealed a significant improvement in sleep structure, elimination of the apnea episodes, and restoration of blood SрO2 after the therapy. Analysis of the serum melatonin vales confirmed a statistically significant increase of melatonin level against baseline in patients with SOAS after the treatment. A correlation analysis showed a relationship between the melatonin level, daytime sleepiness, and blood SрO2.Conclusion. The results of this study and the data of other researchers demonstrate that the elimination of intermittent nocturnal hypoxia in patients with SOAS allows reducing the morning serum melatonin level, thereby reducing the daytime sleepiness and subsequently improving the quality of life.

Changes in lung inflation in asthma in patients with osmotic airway hyperresponsiveness

The scientific literature does not provide enough information on whether bronchial hyperresponsiveness to hypoosmotic stimulus in patients with asthma can lead to more pronounced disturbances of regional lung ventilation.Aim. to characterize lung inflation in asthma patients with osmotic airway hyperresponsiveness.Methods. The lung inflation was studied by body plethysmography, as well as by three-dimensional volumetry, planimetry, and multispiral CT densitometry in 24 patients (group 1) with persistent mild asthma and osmotic airway hyperresponsiveness, identified by the bronchoprovocation test with inhalation of distilled water (IDW) (the average ДРБУ1 was —21.1 ± 3.2%). The comparison group (group 2) consisted of 49 patients with no response to IDW (the average ДББУ1 was —3.7 ± 0.5%; p = 0.00001).Results. Group 1 had lower lung function (FEVj was 83.6 ± 4.5%; FEF50 was 58.1 ± 5.8%) at baseline in comparison with the group 2 (96.7 ± 2.2%, p = 0.0042 and 75.5 ± 2.2%, p = 0.016, respectively) and higher indices of lung inflation at body plethysmography (RV was 153.2 ± 12.5 and 127.5 ± 4.0%, respectively; p = 0,027; RV/TLC was 128.8 ± 5.5 and 109.9 ± 2.8%, respectively; p = 0.015). According to three-dimensional volumetry, the indicators of expiratory lung inflation (526.0 ± 117.8 vox) and average residual inflation of both lungs (13.1 ± 2.6 vox) in group 1 were significantly higher than in group 2 (301.5 ± 55.8 vox, р < 0.05 and 9.1 ± 1.6 vox,р < 0,05, respectively). The patients with osmotic airway hyperresponsiveness also showed higher values of the expiratory area in the middle zone (235.3 ± 29.4 and 149.2 ± 14.9 pix, respectively; p = 0.00 47) and the lower zone (292.3 ± 37.9 and 178.6 ± 18.6 pix, respectively; p = 0.0034) of the lungs.Conclusion. Asthma patients with osmotic airway hyperresponsiveness have lung hyperinflation with impaired lung ventilation predominantly in the middle and lower zones.

Obstructive sleep apnea and cardiovascular comorbidity: modern discordance in assessing the effectiveness of CPAP-therapy against the pathogenetic mechanisms and cardiovascular diseases

Sleep-disordered breathing (and obstructive sleep apnea, OSA) is a common pathology in the general population in economically developed countries. In the last decades, CPAP therapy (continuous positive airway pressure) became the first-choice treatment option in clinically relevant OSA.Objective. The review summarized available evidence about the effects of CPAP-therapy on the main pathogenetic pathways of OSA (sleep-related sympathetic activity, vascular inflammation, endothelial dysfunction, oxidative stress, and blood coagulation) and cardiovascular diseases (CVDs - hypertension, cardiac arrhythmias, heart failure, pulmonary hypertension, coronary heart disease, and combined cardiovascular outcomes, including cardiovascular mortality).Methods. We analyzed the data of the randomized observational cohort clinical trials and metaanalyses, which assessed the effects of CPAP-therapy on the pathophysiological mechanisms of OSA and the associated CVDs. We also analyzed current guidelines on the management of patients with CVDs and OAS. We searched the following databases: Scopus, Pubmed, Google Scholar, Russian Scientific Citation Index.Results. Despite the rather recent implementation of this method, the accumulated evidence shows its favorable impact on OSA pathogenesis (on sympathetic activity and, to some extent, on vascular inflammation and endothelial dysfunction) and CVDs (hypertension, in particular, resistant hypertension, and paroxysmal atrial fibrillation). The observational studies also demonstrate favorable outcomes regarding other CVDs. However, the data of the randomized clinical trials are limited or controversial, the samples are rather small, which leads to inconsistent conclusions.Conclusion. Currently, most of the researchers emphasize that the required CPAP-adherence level (regular use for at least 4 h nightly) is the main barrier to getting the high-level evidence of CPAP efficiency with regard to the cardiovascular risk. This factor becomes the biggest limitation in patients who are characterized by the low compliance because they are not prone to daytime sleepiness.

A new delivery device for benralizumab (autoinjector, pen-injector device) in the clinical practice of treating severe eosinophilic asthma: Conclusion of the Expert Council

The emergence of new means of administering genetically-engineered biological drugs, such as an autoinjector (pen injector device), can positively affect the organizational aspects of treating patients with severe eosinophilic asthma (SA) who need biological therapy.The aim. To determine the place of a new delivery device for benralizumab (autoinjector, pen injector device) in the clinical practice of treating eosinophilic SA.Results. The expert council considered the results of the latest clinical studies and real practice data on the use of genetically-engineered biological drugs in the form of an autoinjector. The experts discussed the safety and efficacy of this delivery device and recommended considering the possibility of switching eosinophilic SA patients to self-administration of genetically-engineered biological drugs (autoinjector form) at home. This treatment tactic is especially relevant in the current epidemiological situation since it will reduce the risks of infection compared to planned medical care in inpatient or outpatient treatment settings and reduce the burden for healthcare workers.Conclusion. The practice of switching eosinophilic SA patients to self-administration of biologics in the form of an autoinjector (pen injector device) can improve the adherence to biological therapy and quality of life of this group of patients.