The purpose of this study was to investigate clinical, functional and laboratory features of the ACOS syndrome (asthmaCOPD overlap syndrome).

Methods. We examined 108 patients: 54 patients with ACOS syndrome and 54 patients with severe asthma.

Results. The ACOS syndrome was characterized by severe course, lower lung function and pulmonary hyperinflation. A high level of systemic inflammatory markers (IL6, TNFα, CRP) was registered in both the groups. An increased neutrophil elastase blood plasma concentration was revealed in patients with the ACOS syndrome that could indicate a role of neutrophils in the inflammation. sCD31/SPECAM1 and CD38 on blood lymphocytes were higher in the ACOS group compared to the asthma group; this could be related to cellular and molecular mechanisms of endothelial dysfunction.

Conclusion: The current knowledge on the ACOS syndrome is insufficient. Clinical course and pathogenesis of this disease require further investigation.

Chronic pulmonary aspergillosis (CPA) is infrequent respiratory disease which is difficult for diagnosis and can complicate other respiratory diseases and conditions. Currently, there are about 240,000 CPA patients in Europe. The most prevalent variant of CPA is chronic cavitary pulmonary aspergillosis (CCPA) which could progress to chronic fibrosing pulmonary aspergillosis (CFPA) when is untreated. Aspergillus nodules and single aspergilloma are less frequent clinical variants of this disease. All clinical variants of aspergillosis could be found in nonimmunocompromised patients with different underlying pulmonary disorders. Subacute invasive pulmonary aspergillosis, which was referred to as chronic necrotising pulmonary aspergillosis, is the most rapidly progressive clinical variant of the infection (< 3 months); it is typically diagnosed in moderately immunocompromised patients and should be treated as invasive aspergillosis. Diagnosis and management of CPA patients were previously described in sporadic guidelines. Due to this, expert group have been convened to develop clinical, radiological and microbiological guidelines. Diagnosis of CPA requires a combination of the following criteria existing for 3 months or more: one or more cavities in the lungs with or without fungal mass inside or nodules found on radiological examination; direct evidence of Aspergillus infection (using microscopic examination or biopsy culturing) or immunological response to Aspergillus spp. and exclusion of alternative diseases. Antibodies against Aspergillus spp. (precipitins) are increased in > 90% of patients. Aspergilloma should be resected if technically possible; videoassisted thoracic surgery is preferable. Chronic cavitary pulmonary aspergillosis requires longterm oral antifungal therapy to improve the patients' health and respiratory symptoms, to arrest haemoptysis and prevent the disease progression. Azole serum concentration and drug interaction should be thoroughly monitored to avoid toxic effects. Haemoptysis could be arrested using therapy with tranexamic acid or bronchial artery embolization; surgical resection of the lung is rarely required. Haemoptysis could indicate therapeutic failure and / or resistance to antifungals. Patients with a single Aspergillus nodule need antifungal therapy only if surgical resection is impossible. Antifungal therapy could be beneficial in patients with multiple Aspergillusis nodules; these patients need careful followup.

The aim of the study was to investigate COPD phenotypes in order to improve treatment efficacy of occupational COPD and comorbidity of COPD and hypertension.

Methods. This singlecenter observational study involved 97 patients with occupational COPD (according to GOLD 2011 criteria) exposed to chemicals (n = 42) or dusts (n = 55) and 103 patients with of COPD and hypertension (according to ESH/ESC 2013 criteria). Comparison groups included patients with 73 smokers with COPD and 99 patients with COPD without hypertension. Phenotypic features of occupational COPD caused by different workrelated factors and comorbidity of COPD and hypertension were described. The obtained results underlie the treatment programs for each group. A singlecenter openlabel comparative study was conducted to evaluate the efficacy of this approach.

Results. Beclometasone/formoterol combination and tiotropium were used for therapy of COPD related to chemical exposure; indacaterol, glycopyrronium and budesonide were used for therapy of dustrelated COPD. Patients with comorbidity of COPD and hypertension were treated with budesonide/formoterol combination and aclidinium. Coprimary endpoints were exacerbation rate and change of FEV1pred. Treatment with beclometasone/formoterol and tiotropium decreased the exacerbation rate, increased FEV1, improved symptoms, and decreased pulmonary hypertension in patients with COPD related to chemical exposure. Treatment with indacaterol, glycopyrronium and budesonide decreased the exacerbation rate, increased FEV1, improved symptoms, and decreased pulmonary hypertension in patients with dustrelated COPD. Treatment with budesonide/formoterol and aclidinium improved lung function, decreased pulmonary hypertension and improved symptoms in patients with comorbidity of COPD and hypertension.

Conclusion. Different risk factors of COPD could be considered as markers of therapeutic response.

Aim. The aim of this study was to investigate an influence of pulmonary ventilation and diffusion disorders on outcome of pulmonary endarterectomy.

Methods. The study involved patients with chronic thromboembolic pulmonary hypertension (CTEPH) with (n = 43) or without (n = 88) chronic obstructive pulmonary disease (COPD). Body plethysmography and lung diffusing capacity measurement were performed in all patients before pulmonary endarterectomy. We analyzed perioperative clinical characteristics, complications and inhospital mortality.

Results. COPD was diagnosed twice more often in patients with CTEPH. Patients with CTEPH and COPD had more severe lung function disorders including more significant reduction in lung diffusing capacity. Comorbidity of COPD and CTEPH significantly increased a risk of respiratory failure in early postoperative period (OR = 2.1 (1.25 – 4.76), p = 0.020), length of hospitalization (p = 0.02), and a risk of inhospital mortality (OR = 4.4 (1.21 – 16.19), p = 0.023). Lung diffusion capacity had an independent predictive value to predict the development of the respiratory failure in early postoperative period (OR = 1.8 (1.08 – 3.57), p = 0.050).

Conclusion. Diagnosis of COPD in patients with CTEPH significantly increased risk of poor outcome of the pulmonary endarterectomy

The aim of this study was to investigate airway inflammation patterns and clinical and functional features of severe uncontrolled asthma.

Methods. The study involved 25 patients aged 45 to 55 years with severe uncontrolled asthma. Medical history was analyzed. Lung function tests, cytological and cytochemical investigation of induced sputum were performed in all patients. Asthma control was assessed using the Asthma Control Test questionnaire.

Results. The patients were divided into groups: with eosinophilic (> 2% of eosinophils; n = 11) or mixed (≥ 2% of eosinophils and ≥ 61% of neutrophils; n = 14) airway inflammation patterns according to induced sputum cytology. Oxidative function of leucocytes according to myeloper oxidase level in the cells and the degree of cytolysis were increased in the mixed inflammation group. More severe symptoms, more frequent asthma exacerbations, a tendency to worse asthma control and lower FEF50 and MEF25–75 were found in the mixed inflammation group. Coldinduced air way hyperresponsiveness was diagnosed in 12 patients of the mixed inflammation group and in 3 patients of the eosinophilic inflammation group. Severity of the disease, lung function abnormalities and coldinduced airway hyperresponsiveness in patients with severe uncontrolled asthma were related to the airway inflammation pattern.

Conclusion. The mixed inflammation pattern was associated to more severe asthma course and worse control of the disease.

The objective of this 5year prospective study was to investigate a clinical role of isolated decrease of DLCO in patients with systemic sclerosis (SS) without pulmonary arterial hypertension (PAH).

Methods. We selected 48 out of 142 patients with SS: 35 (73%) with limited SS and 13 (27%) with diffuse SS. The average length of the disease was 12.9 ± 7.9 years. Inclusion criteria were DLCO < 80% pred., forced vital capacity (FVC) ≥ 80% pred. and systolic pulmonary artery pressure (PAP) ≤ 35 mm Hg according to echocardiographic examination (echoCG). High resolution computed tomography (HRCT), spirometry, DLCO measurement, and echoCG were obtained at baseline and after 4.7 ± 1 year of follow up. All patients were treated with standard therapy.

Results. CT signs of interstitial lung disease (ILD) were found in 43 (89.6%) patients at baseline and newly developed in 3 other patients during the followup. During the followup, lung CT improved in 5 (10.4%) patients and progressed in 15 (31.3%) patients. Over 5 years, FVC did not change significantly (97.6 ± 10.7% and 100.8 ± 18.9%; р = 0.15), while DLCO significantly decreased both in limited and diffuse SS groups (59.8 ± 13.5% and 56.3 ± 12%; р = 0.006). Mean PAP values remained within normal range in majority of patients. Clinically significant FVC reduction (≥ 10%) was found in 5 patients; of them, CT signs of ILD at baseline were seen in 3 patients and newly developed during the followup in 2 others. Clinically significant DLCO reduction (≥ 10%) was documented in 11 (23%) patients, all had CT signs of ILD at baseline, although CT progression during the followup was noted only in six of them. Contemporary deterioration in FVC, DLCO and CT was found in 3 patients.

Conclusion. Clinical course of ILD in SS patients with isolated DLCO reduction and without PAH was relatively benign, with respiratory volumes being preserved within normal range for long time. Comparison of radiological and functional changes in a prospective study has suggested that DLCO is a more sensitive tool to determine ILD progression compared to HRCT. Regular DLCO measurements could be used as a reliable tool for monitoring of ILD associated with SS.

The aim of this study was to diagnose and to describe chronic obstructive pulmonary disease (COPD) in HIVinfected persons serving sentence in the institutions of the Federal Penitentiary Service (FPS) of Kirov region.

Methods. This was a crosssectional nonrandomised singlecenter study involving 30 HIVpositive hospitalised patients in a FPS medical institution. Clinical examination, chest Xray, MRC scale, CATtest, Fagerström test, CCQ questionnaire, and lung function tests were used in all patients.

Results. Almost a half of patients (16 of 30) had FEV1 / FVC < 70%. Those patients with were more likely to have COPD according to COPD questionnaire.

Conclusions. COPD is underdiagnosed in penitentiary medical institutions. Clinical findings are not sufficient to support this diagnosis. If spirometry is not available, COPD questionnaire could be useful to screening for COPD.

Wheezing is the most common clinical sign and one of the key diagnostic criteria of asthma. Pathophysiology of wheezing is not fully recognized. A theory of hemodynamic flatter is widely adopted. Effects of vibration are actively investigated in patients with snore and obstructive sleep apnea. Vibration can contribute to the upper airway inflammation and endothelial dysfunction in snoring patients. Therefore, the flatter (vibration) effect could be the key mechanism of wheezing in asthma patients and could promote similar changes in the lower airway microvasculature. Recently, CPAP therapy has been shown to reduce asthma symptoms and bronchial hyperresponsiveness and acts as a mechanical bronchodilator is patients with asthma without sleepassociated breathing disorders.

Pulmonary hypertension (PH) is a relatively common complication of sarcoidosis. In different studies, prevalence of PH in sarcoidosis varies from 6% to 74%. PH associated with sarcoidosis (PHAS) is typically associated with poor prognosis. Though PHAS is diagnosed more often in patients with advanced sarcoidosis, it could occasionally occur without pulmonary parenchymal lesions. Pathophysiology of PHAS is quite complex and includes several mechanisms including pulmonary fibrosis, hypoxic vasoconstriction, pulmonary vascular granulomatous obliteration and / or angiitis, extrinsic pulmonary vascular compression, pulmonary venoocclusive disease, and left heart disease. Management of PHAS is based on treatment of hypoxemia, active sarcoidosis and comorbidities. A role of systemic steroids in therapy of PHAS remains controversial. Pulmonary arterial hypertension (PAH) specific therapy has not been yet recommended in PHAS, but prostanoids, endothelin receptor antagonists and phosphodi esterase5 inhibitors were effective in some patients with PHAS in several small trials. Additional welldesigned randomized placebocontrolled studies are needed to investigate a role of PAHspecific therapy in certain cohorts of patients with PHAS.

Glucocorticoids are widely used for the treatment of chronic obstructive pulmonary disease (COPD) because of their antiinflammatory properties. However, their therapeutic effectiveness is significantly limited in COPD. Molecular mechanisms of steroid resistance include defective glucocorticoid receptor (GR) binding and translocation into the nucleus, increased expression of GRβ isoform, elevated expression of macrophage migration inhibitory factor (MIF), decreased expression of mitogenactivated protein kinase phosphatase 1 (MKP1) and histone deacetylase 2 (HDAC2). HDAC2 is involved in suppression of inflammatory genes by glucocorticoids, and its reduced activity and expression are the result of oxidative and nitrative stress induced by cigarette smoke. Oxidative stress causes activation of phosphoinositide3kinase δ (PI3Kδ) which leads to phosphorylation (activation) of Akt kinase, phosphorylation (inhibition) of glycogen synthase kinase 3β and phosphorylation (inactivation) of HDAC2. Understanding of the mechanisms leading to steroid resistance allowed identification drugs targeting this condition. Antidepressant nortriptyline and macrolide solithromycin reverse corticosteroid resistance through inhibition of Akt phosphorylation. Combination of glucocorticoid and longacting β2agonist increases GR nuclear translocation and inhibits Akt phosphorylation. The phosphodiesterase 4 inhibitor roflumilast in combination with dexamethasone improves steroid responsiveness through modulation of PI3Kδ, HDAC2, MKP1, MIF and GRβ expression. Investigation of the molecular mechanisms of steroid resistance can increase antiinflammatory properties of steroids and lead to more effective COPD treatment.

Mannosebinding lectin is a part of the innate immunity that, being the first barrier of the antiinfectious defense, acts in first minutes or hours after pathogen challenge. The review provides data about mechanisms of action of mannosebinding lectin and its particular pathogenic role in a wide range of respiratory diseases: bacterial pneumonia, viral respiratory tract infections, tuberculosis, cystic fibrosis, chronic obstructive pulmonary disease, and asthma in adults and children.

This review describes unique components of nitric oxide (NO) cycle in humans. The NO cycle involves NOsynthase, NOsynthase independent component and oxidationreduction reactions. Substrates for NO synthesis could be nitric oxides, nitrite and nitrate anions, organic nitrates, and food nitrates and nitrites. A role of human microbiota has been discussed. A role of important components of nitrite reductase and nitrate reductase systems in the NO cycle, activation and deactivation mechanisms were also described including enzymes, cofactors, homeostasis parameters, etc. These findings help to understand regulatory mechanisms of NO cycle that is important for targeted treatment.

Mucolytics with efficacy approved for cystic fibrosis (CF) have been reviewed by the authors. Currently, investigators search for new mucoactive agents to improve sputum rheology and expectoration in CF. One the promising mucolytics is inhaled dry powder mannitol which was effective and safe in several international trials. Inhaled mannitol has been implemented in clinical practice for CF treatment in some countries. Therefore, goals of new studies should be optimization the use, determination the target population and investigation of combined therapy with different mucolytics in CF.

Idiopathic pulmonary fibrosis (IPF) is the most common clinical variant of idiopathic interstitial pneumonia. Pathophysiology of IPF involves recurrent damage of the alveolar epithelium with fibroblast excessive proliferation as aberrant reparative activity of the lung interstitium. Currently, a treatment approach to this disease has been revised. Given new knowledge on pathogenesis of IPF, an international evidencebased clinical guideline published in 2015 recommends antifibrotic agents as the basic therapy of IPF. The only antifibrotic agent registered in Russia is niintedanib. A clinical case of IPF with the first experience of therapy with nintedanib in Omsk region has been reported in the article.