EDITORIAL
Recently, bitter taste receptor (TAS2R) expression has been found in the respiratory system, but function of these receptors is largely unknown. The aim of our study was to assess serum concentration of TAS2R38 bitter taste receptors in patients with asthma. Methods. We examined 49 patients with asthma and 33 healthy individuals. Asthma was diagnosed according to GINA, 2016. Bitter taste receptor (TAS2R) expression was measured in paired samples using the immunoenzyme analysis. Results. Bitter taste receptor (TAS2R) expression levels significantly differed between healthy males and healthy females with the highest values in females. Bitter taste receptor (TAS2R) expression level was twice lower in female patients with atopic asthma compared to the healthy females. This parameter did not differ significantly between both males and females with non-atopic asthma compared to controls and to atopic asthma patients. Serum concentration of TAS2R38 bitter taste receptors was related to blood cell counts (lymphocytes, monocytes, neutrophils). In patients with non-atopic asthma, serum concentration of TAS2R38 bitter taste receptors was related to sputum count of ciliated cells. TAS2R38 receptor concentration was also related to some infectious upper airway diseases (pharyngitis, tonsillitis) in females with atopic asthma. Lung function parameters (peak expiratory flow and the maximal expiratory flow at 50% of the forced vital capacity) were inversely related to TAS2R38 receptor concentration. Conclusion. We suppose that soluble serum TAS2R38 bitter taste receptors could probably act as negative regulators and contribute to the inflammation in asthma.
CLINICAL GUIDELINES
Pulmonary hypertension (PH) is a pathophysiological condition which could develop in many diseases. PH could also complicate majority of cardiovascular and pulmonary diseases. This guideline was developed by European Society of Cardiology (ESC) and European Respiratory Society (ERS). The aim of this guideline was to integrate majority of recent studies and to create educational tools and programmes for implementation of these recommendations into clinical practice. The authors made a systematic review of studies published in Medline database since 2009. An updated common classification for PH in adults and children is included in this guideline. New haemodynamic definition of pulmonary arterial hypertension involves pulmonary vascular resistance. This guideline includes novel findings on pathology, pathobiology, genetics, epidemiology, and risk factors. The authors updated a diagnostic algorithm and screening strategy, and described recent achievements in evaluating severity and therapy of PH including combined treatment. Also, a new short chapter on PH with unclear and/ or multifactorial mechanisms was added.
ORIGINAL STUDIES
The aim of this study was to analyze an association between TLR1 and TLR6 gene polymorphism and development of bronchial asthma in Russian patients living at the Republic of Bashkortostan.
Methods. We investigated DNA samples of unrelated individuals (n = 179) and healthy volunteers (n = 121) of Russian ethnic group. DNA was extracted by phenol-chlorophorm extraction. Genotyping of polymorphic variant was performed by the real-time polymerase chain reaction.
Results. An association between rs5743571 polymorphism in the TLR1 gene and rs5743794 polymorphism in the TLR6 gene with occurrence of bronchial asthma has been found.
Conclusion. TLR1 and TLR6 genes are important for asthma susceptibility in Russian population. Polymorphism in rs5743571*C allele and rs5743571*CC genotype of TLR1 gene could be used as high-risk markers; rs5743571*CT genotype of this polymorphic variant could be used as low-risk marker of asthma occurrence. These results can improve our knowledge on defensive mechanisms against atopic sensitization including TLR2 heterodimers and subsequent development of atopic asthma.
This study was aimed at evaluation of pathogenic role of Fохр3, GATA-3, c-Maf, and T-bet transcription factors in asthma.
Methods. 47 healthy individuals and 82 patients with bronchial asthma including 42 patients with allergic asthma (ABA) and 40 patients with non-allergic asthma (NABA) participated in the study. An expression of mRNA of Fохр3 (forkhead box P3), с-Maf (transcription factor Maf), GATA3 (GATA-binding protein 3), and T-bet (T-box protein, TBX21) transcription factors was evaluated by reverse transcription polymerase chain reaction (RT-PCR). Serum concentrations of IgE and cytokines (IL-4, IL-13, IL-17, IL-6, IFN-γ) were measured using ELISA method.
Results. An imbalance in Th1/Th2/Foxp3+Treg and Th17/Foxp3+Treg systems was found in patients with asthma. Foxp3 mRNA expression was decreased in asthma patients compared to healthy individuals. This could probably reflect an impaired regulatory role of Treg in asthma. At the same time, asthma severity was related to concentrations of Foxp3 mRNA and IL-17 and IL-6. This inverse relationship could indicate an imbalance between Foxp3+Treg and Th17 towards the increase in Th17 activity and the reduction in Foxp3+Treg cell number in asthma. Blood mononuclear cells of ABA patients were characterized by significantly increased expression of mRNA of c-Maf and GATA3 Th2-specific transcription factors, associated cytokines (IL-4, IL-13) and IgE. Nevertheless, ABA patients had lower T-bet expression compared to healthy individuals and NABA patients.
Conclusion. Asthma worsening in NABA patients was associated with reduced T-bet mRNA expression and increased GATA3 mRNA expression. This could be due to Th1/Th2-cell imbalance towards the increased Th2-response.
The aim of this study was to determine a relationship between IL-17, IL-10 and vitamin D concentrations and asthma control level in adult patients.
Methods. This was a comparative study which involved 79 asthma patients. The patients were divided in two groups: 48 patients with good control of asthma (mean age, 52 ± 13 years; BMI, 24.9 (21.6 – 28.3) kg/m2) and 31 patients with uncontrolled asthma (mean age, 57.6 ± 7.9 years; BMI, 29.1 (27.3 – 33.6) kg/m2). Concentrations of IL-10, IL-17 and vitamin D were measured in blood serum using ELISA assay.
Results. Vitamin D concentration was significantly lower in patients with uncontrolled asthma compared to well-controlled asthma. An inverse relationship was found between vitamin D and IL-17 blood concentrations but not between vitamin D and IL-10 blood concentrations.
Conclusion. Serum concentration of vitamin D could be used as a predictor of asthma course and control.
The aim of this study was to evaluate the upper gastrointestinal tract in patients with asthma and to investigate relationships between the diagnosed digestive abnormalities and asthma course.
Methods. Asthma clinical signs, bronchial obstruction, severity of inflammation, immunological reactivity, and endoscopic characteristics of esophagus, stomach, and duodenum were studied in patients with asthma and comorbid diseases of the upper gastrointestinal tract (the study group; n = 124) and in patients with asthma without clinical signs of digestive disease (the comparator group; n = 23).
Results. Asthma course, inflammation and immunological abnormalities were more severe in patients with digestive disorders. Inflammation, atrophy and gastrointestinal motility changes were seen during endoscopy.
Conclusion. These abnormalities were related to clinical features of asthma, severity of bronchial inflammation and immunological disorders.
The objectives of this study were to estimate prevalence of asthma-like symptomsand allergic rhinitis in preschool children and to determine risk factors of these diseases.
Methods. This cross-sectional study was conducted in 5 cities of Altai krai in 2015 – 2016 and included children aged 3 to 6 years. Prevalence of allergic diseases was assessed using the Russian version of the ISAAC questionnaire.
Results. The prevalence of asthma-like symptoms was 11.1%, and the prevalence of allergic rhinitis was 18.0%. The diagnoses of asthma and allergic rhinitis were physician-confirmed in 0.9% and 6.4% of 3205 children, respectively. Family history of allergic diseases was related to the increased risk of asthma-like symptoms (ОR 2.11; 95% CI 1.66 – 2.68) and allergic rhinitis (ОR 2.63; 95% CI 2.16 – 3.19). Boys also had the increases risk of asthma-like symptoms (OR 2.63; 95% CI 1.17 – 5.93) and allergic rhinitis (ОR 1.35; 95% CI 1.01 – 1.37). Smoking in parents during the first year of life of the child increased the risk of asthma-like symptoms (ОR 1.61; 95% CI 1.15 – 2.24).
Conclusion. The prevalence of asthma-like symptoms and allergic rhinitis considerably exceeds the rate of physician-confirmed diagnosis. Family history of allergic diseases, male gender, and smoking in parents increased the risk of allergic diseases in preschool children.
The aim of this study was smoking modeling with visualization of microparticles of the smoke deposed on the walls of the digestive and the respiratory tracts.
Methods. Patients with tuberculosis and chronic non-infectious lung diseases participated in the study. All the patients underwent bronchoscopy. Powdered tantalum mircoparticles with the size of < 1 µm were used as markers of tobacco smoke microparticle deposition. The tantalum powder was administered orally and intratracheally. Tantalum microparticles deposed in the airways were identified using the chest X-ray examination immediately and in 4 h after the insufflation.
Results. In most patients (64.3%), 95% of microparticles deposed in the mouth, the oropharingeal area, the pharynx, the pyriform sinuses and the larynx just after the insufflation and only 5% achieved the lower airways.
Conclusion. We investigated factors facilitating deposition of microparticles into the bronchi. Such deposition could lead to bronchial obstruction and further penetration of microparticles into the alveoli. We also determined three types of optical density of the deposed smoke microparticles that could characterize microparticle layer thickness, a mechanism of deposition (impaction, sedimentation, or diffusion) and its distinct location.
The aim of this retrospective single-center continuous study was to investigate structure, characteristics and abilities to predict regional drug resistance of Mycobacterium tuberculosis in a therapeutic facility of Federal Penitentiary Service of Russia.
Methods. Sputum samples of all patients with newly diagnosed, recurrent or previously treated tuberculosis admitted to a tuberculosis hospital in 2007 – 2015 were cultured.
Results. Data on structure and changes in primary (PDR), multiple (MDR) and broad-spectrum (BSDR) drug resistance of Mycobacterium tuberculosis in newly diagnosed tuberculosis patients, secondary (SDR), MDR and BSDR of Mycobacterium tuberculosis in patients with recurrent tuberculosis are presented in the article. Proportion of newly diagnosed tuberculosis patients with drug resistance increased from 50.7% to 72.9%. MDR increased from 12.1% to 40.4%, and BSDR increased from 1.3% to 11.4% in this group of patients. Proportion of patients with recurrent tuberculosis and with drug resistance increased from 54.5% to 100%. In these patients, MDR increased from 41.7% to 81.3%, and BSDR increased from 4.3% to 41.7%. In patients with previously treated tuberculosis, SDR increased from 79.3% to 96.8%, MDR increased from 31.1% to 76.8%, and SBDR increased from 5.9% to 39.7%.
Conclusion. A high level of PDR, growth of MDR and gradual increase in BSDR are expected. An explanation of this process is long-term treatment of chronic tuberculosis in penitentiary service that facilitates development of consistent population of Mycobacterium tuberculosis with significant drug resistance.
REVIEW
In most case, lung lesions of different character and extent remain after successful treatment of pulmonary tuberculosis. High tuberculosis morbidity contributes to increasing numbers of patients with post-tuberculosis abnormalities. Pulmonary tuberculosis or its consequences could cause consistent changes of the lung function. Lung function abnormalities in patients survived pulmonary tuberculosis have been reviewed In this article. A high prevalence of such cases provides the need in spirometric testing. Routine identification of patients with post-tuberculosis pulmonary impairment requires revision of recommendations for spirometry use in tuberculosis patients.
This is a review of published data on oxidative stress-induced antibiotic resistance of pathogens caused by antimicrobials. Known mechanisms of oxidative stress in a bacterial cell include occurrence of oxygen reactive species, protein oxidation products, fat acids, intracellular molecular oxygen and transition metal ions. Investigations of bacterial antioxidant defense under antibiotic-induced oxidative stress are at an early stage. Understanding the relationship between oxidative stress and bacterial resistance to antibiotics could facilitate development of novel antimicrobials due to both stimulation of oxidation properties of antimicrobials and searching new ways for inhibition of antioxidant defense of pathogens.
CLINICAL PHARMACOLOGY
The Salford Lung Study in asthma (SLS-Asthma) is the first prospective, randomized, controlled clinical trial conducted in conditions and in population that were very close to real clinical practice. The study demonstrated that treatment of a large heterogeneous population of asthma patients using combination of vilanterol (VI) and fluticasone furoate (FF) (22/92 mg q.d. or 22/184 mg q.d.) via Ellipta dry powder inhaler provided better control of the disease than the conventional therapy administered by an attendant physician. The level of asthma control in VI/FF group was consistently maintained for 12 months with no identified change in risk of development of serious adverse events. Results were similar in patients receiving ICS or ICS/LABA combinations and did not depend on smoking status or number of exacerbations over the previous year.
ANNIVERSARIES
PRACTICAL NOTES
Lung injury is a common extra-articular manifestation of rheumatoid arthritis (RA). Lung involvement is usually characterized by insidious onset, but has poor prognosis with significant worsening in patients' quality of life, disability and often fatal outcome. Lung injury could be caused both by the rheumatoid disease, drug toxicity and opportunistic infection related to immunosuppression. Active screening using high-resolution computed tomography (HRCT) of the lungs revealed frequent subclinical pulmonary abnormalities, but their prognostic role remains unclear. Moreover, HRCT does not allow differentiating between RA-associated lung injury and drug toxicity. Currently, overestimation of drug-induced lung injury and underestimation of rheumatoid disease as a cause of lung damage are often seen in clinical practice. A case report presented in this article demonstrates pulmonary involvement in rheumatoid disease.
OBITUARY
ISSN 2541-9617 (Online)