Recent investigations in immunology resulted in recognition of diseases related to abnormal synthesis of immunoglobulin G (IgG). IgG plays the key role for human defense from pathogens and foreign particles. The biological function of IgG is to initiate opsonisation of pathogens. Another important function of IgG is activation of the complement. As a biological marker, IgG could be used for diagnosis of recurrent infections of lower and upper airways, asthma, bronchiectasis, vasculitis, multiple myeloma, etc. This review is aimed at a role of both IgG deficiency and hyperproduction for diagnosis and treatment of various diseases. Prevalence of IgG deficiency was investigated in epidemiological studies, both in population level and in selected groups of patients with recurrent respiratory infections. The results showed susceptibility to Streptococcus pneumoniae, Haemophilus influenzae-b, and Neisseria meningitidis, infections in patients with IgG2 deficiency. The most common diseases were of it media, sinusitis, and recurrent bronchitis. Pneumonia and meningococcemia occurred in severe cases. Bronchiectasis occurred in patients with frequent episodes of respiratory infection. A selective increase in IgG4 level is particularly important as it is associated with development of idiopathic fibrosis. Retroperitoneal fibrosis, autoimmune pancreatitis, sclerosing cholangitis, salivary gland hypertrophy, sialadenitis, interstitial pneumonias, etc., were reported. This is the first article in a series of publications about IgG-related diseases. Pathogenesis, clinical symptoms and therapy of fibrosis associated with IgG4 hyperproduction have been described in the review. Further publications will discuss other IgG-related diseases.

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.

The aim of the study was to estimate the contribution of angiotensinogen (AGT), transforming growth factor beta-1 (TGFB1), estrogen receptor alpha (ESR1), and vitamin D receptor (VDR) gene variants to IIP and PS development and course in residents of Russian Federation. Methods. This case-control study involved 104 IIP patients, 111 PS patients, and 113 controls. Seven single nucleotide polymorphisms were investigated using polymerase chain reaction followed by restriction analysis, namely rs5051 in AGT gene; rs1800469, rs1800470, and rs1800471 in TGFB1 gene; rs2234693 and rs9340799 in ESR1 gene; rs731236 in VDR gene. Results. We revealed associations of TGFB1 (rs1800469) and ESR1 (rs9340799) gene variants with IIP clinical outcomes, as well as AGT (rs5051) and VDR (rs731236) gene variants with PS stage. Unfavorable IIP outcomes, i.e. IIP progression or death, were associated with variants rs1800469 СС in TGFB1 gene (р = 0.021; odds ratio (OR) = 2.83; 95%CI: 1.16–6.94) and rs9340799 X (G) in ESR1 gene (р = 0.012; OR = 3.18; 95%CI: 1.27–8.00), as well as with their combination (р = 0.003; OR = 3.88; 95%CI: 1.55–9.71). PS stages II–IV were associated with variants rs5051 А in AGT gene (р = 0.010; OR = 3.22; 95%CI: 1.30–7.98) and rs731236 t (C) in VDR gene (р = 0.046; OR = 2.45; 95%CI: 1.00–6.02), as well as with their combination (р = 0.041; OR = 3.31; 95%CI: 1.14–9.60). Conclusion. Results of the study contribute to understanding genetic factors that influence IIP and PS courses.

The aim of this study was to investigate clinical course, survival and predictors of mortality in patients with chronic obstructive pulmonary disease (COPD) with or without pulmonary hypertension (PH). Methods. The study involved 288 patients with COPD (276 males, 12 females; mean age, 59.50 ± 9.27 years; smoking history, 23.10 ± 11.42 pack-years; body mass index, 27.20 ± 12.06 kg × m-2; the annual exacerbation rate, 2.40 ± 0.89), GOLD stage, II – IV (GOLD, 2016). PH was diagnosed if resting systolic pulmonary artery pressure (sysPAP) measured by Doppler echocardiography was > 40 mm Hg. The patients were divided on three groups: those without PH (sysPAP < 40 mm Hg; n = 168), those with moderate PH (sysPAP, 40 – 55 mm Hg; n = 101), and those with severe PH (sysPAP > 55 mm Hg; n = 19). Results. Increased sysPAP was found in 120 patients (41.7%) including 101 patients with moderate PH (35.1%) and 19 patients with severe PH (6.6%). Clinical symptoms of PH were more prominent in COPD patients with severe PH. Clinical symptoms assessed by CAT and Borg's scales, COPD exacerbation rate, the right atrium size, sysPAP, blood levels of C-reactive protein, fibrinogen, NT-proCNP and NT-proBNP predicted mortality of patients with COPD and PH. Survival of COPD patients with PH depended on PH severity. Conclusion. In most patients with COPD and PH, PH was moderate. PH aggravated severity of clinical signs and symptoms and increased the risk of mortality. In-hospital survival of patients with COPD and PH depended on PH severity.

The aim of this study was to evaluate a role of presepsin for diagnosis of severe pneumonia and sepsis. Methods. The study involved 54 patients with pneumonia, sepsis, and other inflammatory diseases, aged 17 to 77 years. Presepsin level was measured in all the patients using immunochemiluminescent analysis. Before entering the study, all patients were treated with antibacterials in other healthcare institutions. Results. Presepsin level was 3083.8 ± 598.1 pg/mL in patients with pneumogenic sepsis (n = 14), 2867.40 ± 503.64 pg/mL in patients with abdominal sepsis (n = 16), and 873,00 ± 132.92 pg/mL in patients with other inflammatory diseases (n = 8). Preseptin level was 5430.50 ± 721.97 pg/mL in patients with severe pneumogenic sepsis (n = 4) compared to 1471.7 ± 221.8 pg/mL in those with non-severe pneumogenic sepsis (n = 6; p < 0.05) and 642.00 ± 140.59 pg/mL in patients with severe pneumonia (n = 10) compared to 231.30 ± 54.26 pg/mL in patients with non-severe pneumonia (n = 6; p < 0.05). Conclusion. A high level of presepsin could be used as a marker of active infection as it reflects severity of pneumonia and sepsis.Persistent high level of presepsin under antibiotic treatment could indicate failure of the therapy. Therefore, presepsin could be used as a reliable diagnostic marker which helps to determine severity of pneumonia and sepsis, and therapeutic efficacy.

The aim of the study is to assess the quality of diagnosis made by the primary care physicians of Krasnodarski krai in patients with idiopathic pulmonary fibrosis (IPF) admitted to the Pulmonology Department of our hospital for the period of 2013 – 2015. Methods. A retrospective analysis of 83 medical records (form 003-U) of patients with IPF diagnosed in our Department has been performed. Men (63.86%) over the age of 50 years (90.37%) prevailed in the study. The most frequent concomitant conditions in patients with IPF were ischemic heart disease (20.48%), hypertension (16.87%), and gastroesophageal reflux disease (15.66%). In the presence of typical clinical picture, the diagnosis of IPF was suspected by primary care physicians in 22.89% of patients. Results. It was revealed that underdiagnosis of diffuse reticular changes, honeycombing, traction bronchiectasis and overdiagnosis of bilateral infiltration of the lung tissue, bilateral small focal formations, and ground- glass opacities took place in interpreting of CT images by primary care radiologists. Conclusion. In most patients the diagnosis of IPF is established for the first time at the stage of «honeycombing», which indicates late diagnosis of the disease.

The purpose of this study was to analyze prospectively clinical and economic effects of vaccination of COPD patients using conjugated pneumococcal vaccine PСV13 (Prevenar 13). Methods. The study involved 394 male patients treated in the Teaching Hospital No.4 and Chelyabinsk Pulmonary Center in 2012 – 2016. Number of COPD exacerbations, hospitalizations and cases of pneumonia was analyzed; dyspnea and lung function were also measured; BODE, DOSE, and ADO prognostic indices were calculated. The cost-efficacy of vaccination was assessed. Results. Vaccination with PСV13 vaccine allowed stabilization basic respiratory functional parameters. In a year after the vaccination, BODE, DOSE, and ADO indices significantly decreased and this effect maintained during four years. Number of infectious exacerbations and pneumonia cases significantly decreased in 4 years after vaccination in non-smoking patients. Conclusion. The prognostic indices are a reliable tool to evaluate efficacy of treatment. Vaccination allowed saving up to RUR 394.3 million (78.5%) per a year due to reduction in number of COPD exacerbations and rate of pneumonia.

The aim. This study was aimed at assessment of clinical efficacy, tolerability and safety of two fixed combinations: Salticasone Aeronativ (salmeterol + fluticasone) 25/125 µg(Russia) compared to Seretide® 25/125 3 µg (GlaxoSmithKline Pharmaceuticals C.A., Poland) in patients with uncontrolled and partly controlled asthma. Methods. This was a multicenter open randomized clinical trial involving two groups of patients at 1 : 1 ratio: patients treated with Salticasone Aeronativ or Seretide®, two doses b.i.d. during 12 weeks. The primary endpoints were change in FEV1 from the baseline to the end of the study and proportion of patients achieving good asthma control to the end of the study according to ACT questionnaire. The secondary endpoints were change in the peak expiratory flow rate from the baseline to the end of the study; the average daily number of inhalations of short-acting beta-agonists as needed according to the patient’s dairy; time to the first exacerbation of asthma; asthma control level according to ACT questionnaire; change in asthma control according to ACQ questionnaire; change in quality of life according to AQLQ questionnaire; number of asthma exacerbations or seek for emergency care during the study. Results. One hundred and sixteen patients were included in the study, 58 patients in each group. The maximal length of the therapy was 98 days. Two groups did not differ significantly in all the primary and secondary end-points at baseline or in 12 weeks of therapy. The peak expiratory flow rate, asthma control level and quality of life improved equally in both the groups to the end of the study. Conclusion. The Russian combined aerosol inhaler Salticasone Aeronativ (salmeterol + fluticasone), 25/125 µg is equally effective as Seretide® 25/125 µg (GlaxoSmithKline Pharmaceuticals C.A., Poland) in patients with uncontrolled and partly controlled asthma. Salticasone Aeronativ has the similar safety profile and tolerability as Seretide®.

The aim of this study was to describe immunocompromised patients admitted in a multi-profile hospital. Methods. Risk factors, morbidity, treatment, prevention and mortality of immunocompromised patients were analyzed. Results. Immunocompromised patients included patients with primary immunodeficiency, diabetes mellitus, kidney transplant recipients, Crohn’s disease and patients treated with immunosupressors. Patients generally had moderate to severe course of the disease. Conclusion. The proportion of immunocompromised patients in a multi-profile hospital as high as 80%. Infectious complications and prevention of infections is important in those patients and require additional analysis.

The article provides a review of key studies of the hypothesis about an independent pulmonary mechanical activity: from phylogenic analysis of respiratory movements in amphibians and mammals to respiratory mechanics research. The airflow interruption method revealed negative elastic lung hysteresis. Given the basic physical laws (the first and the second laws of thermodynamics), this paradox was considered as evidence of the independent mechanical activity of the lungs. Predominance of breathing-related pressure fluctuations in an obstructed bronchus over the intrathoracic pressure amplitude was considered as a manifestation of the regional pulmonary mechanical activity. Experimental studies of respiratory mechanics allowed formulation a hypothesis about three levels of pulmonary mechanical activity. The integral pulmonary mechanical activity provides inspiratory and expiratory movements. Smooth muscles of the bronchial wall keep the bronchial lumen during expiration and preclude valvular obstruction of the bronchus (the second level of the mechanical activity). The inspiratory action of the smooth muscles in distal parts of the lungs is a functional component along with surfactant that provides the consistency of alveoli during expirations (the third component).

Authors analyzed recently published data and own study results on influence of particulate matter (PM) of different size, origin and chemical composition on the human respiratory system. Traffic-related air pollution is particularly dangerous as it contains transition metals. Short-term exposure of high concentrations of fine particles was associated with an increase in number of hospitalizations and mortality from chronic lung diseases. Long-term exposure of such particles was associated with development of chronic obstructive pulmonary disease, asthma, and lung carcinoma. PM-induced oxidative stress is the key trigger of inflammation. Reactive oxygen species stimulate production and release of cytokines from the cells including bronchial and the lung tissues. The oxidative stress can change the epithelial cell permeability that leads to DNA damage, lipid peroxidation, protein modification, and other disturbances, which facilitate development of chronic lung diseases. There is a need to systematize the available results and better understand the role of PM air pollution for pathogenesis of the respiratory diseases.

The most common lung function abnormalities in patients with respiratory diseases have been reviewed in the article. Ventilation disorders with change in the lung volumes, bronchial obstruction and hypoxemia are typical for patients with pneumonia. Lung compliance reduction, inconsistency of ventilation, and ventilation perfusion mismatch could be found in chronic non-obstructive bronchitis. Chronic obstructive pulmonary disease is associated with bronchial obstruction which is defined as decreased forced expiratory volume for 1 sec (FEV1) and forced expiratory flows at different levels of forced vital capacity (FVC) and increased airway resistance. Asthma is associated with reversible change in expiratory flows, such as FEV1 and peak expiratory flow, due to bronchial hyperresponsiveness. Residual volume (RV) could increase in patients with acute asthma attack. Emphysema is characterized by changes in lung volumes, primarily due to increased RV; lung diffusing capacity (DLCO) could decrease and the lung perfusion could change. Mixed (obstructive and restrictive) lung ventilation disorders could be diagnosed in patients with chronic purulent lung diseases. Patients with disseminated lung lesions could demonstrate decreased lung compliance, reduced lung volumes, decreased DLCO and hypoxemia without hypercapnia.

Langerhans cell histiocytosis (LCH) is a heterogeneous group of diseases with typical accumulation of Langerhans cells in different organs and tissues and formation of granulomas with eosinophil infiltration. Pulmonary LCH in adults is an orphan interstitial lung disease. This disease could occur independently on 15% or to be a part of a multisystemic disease in similar proportion of cases. The clinical course of LCH is various and unpredictable and could vary from asymptomatic course to severe progressive pulmonary injury and respiratory failure. The disease could regress spontaneously in a quarter of patients; have the stable course in 50% and progress in 25% of patients. A case of early-stage pulmonary LCH in a 73-year-old smoker was reported in the article. The diagnose was made according to histological and immunohistochemical investigations of VATS biopsy of the lung tissue. Disseminated injury of the lungs without cysts was found that is typical for early stage of LCH and is difficult for detection. Radiological follow-up revealed rapid progression of the disease.

A clinical case of 48-year-old man with recurrent thrombosis of small pulmonary arteries (PA) has been described in the article. Hereditary and acquired thrombophilia associated with mutations of plasminogen activator inhibitor (heterozygote of the PAI-1 4G / 5G polymorphism) and platelet fibrinogen receptor (heterozygote of the ITGB3 Leu33Pro polymorphism), hyperhomocysteinemia, and hypercholesterolemia was diagnosed. The diagnosis was confirmed by measurement of blood homocysteine and cholesterol levels, and molecular investigation of gene polymorphism mentioned above. PA thrombosis and thrombus location were detected using contrast-enhanced chest computed tomography. Conservative treatment resulted in clinical and radiological improvement.

Synthesis, manufacturing and clinical trials of sulfonamides during the Great Patriotic War is a glorious page of Russian pharmaceutical industry and clinical medicine. Sulfidine, the active sulfonamide, was synthesized in 1937 under the stewardship of I.Y.Postovsky. Sulfidine manufacturing was organized in 1942. Pharmacokinetics and pharmacodynamics of sulfidine were investigated in a number of studies of the time. Blood concentration of sulfidine reached 0.88 – 3.10 mg/dL within 4 h after a single oral dose of 1 – 3 g. The peak concentration was observed in 8–12 h and was held at this level within 8 – 16 h. To achieve clinical effect, researchers recommended maintaining sulfidine concentration ≥ 3 –4 mg/dL during 3 or 4 days. The oral administration of sulfidine was associated with gastrointestinal adverse events in 31% of patients; skin rash in 7% of patients, and polyneuritis in one patient. Therefore, Soviet investigators developed intravenous formulation of sulfidine. Pneumonia treatment with i.v. sulfidine required 0.75 – 3.0 g of the drug compared to 24 g of oral formulation. I.v. sulfidine caused less adverse events and similar clinical effect compared to the oral route of administration. Sulfidine treatment of pneumonia led to outstanding results including dramatically decreased mortality from 30% to 4 – 6%. A valuable experience of development and implementation of antibacterial drugs during the Great Patriotic War could be used for revival of the Russian national pharmaceutical industry.