The aim of this study was to analyze inflammation features and possible causes of asthma-COPD overlap syndrome (ACOS). Methods. Clinical examination was performed for all patients included in the study. Blood levels of alpha-1-antitripsin (AAT), immunoglobulin (Ig) G and E antibodies against four bacterial antigens (Streptococcus pneumoniae, Haemophilus influenzae, Neisseria perflava, and Staphylococcus aureus), and lung function were measured in all the patients. Results. The study involved 175 patients including 78 patients with bronchial asthma, 39 patients with ACOS, 38 patients with COPD, and 20 healthy individuals. AAT blood level was reversely related to lung function and to increased IgG-antibody levels against bacterial antigens. Conclusion. Due to this fact, the authors suppose that the ACOS should be considered as an independent nosology distinct from asthma and COPD, and related to microbial inflammation and AAT level.

Adopted from: Woolhouse I., Bishop L., Darlison L., De Fonseka D., Edey A., Edwards J., Faivre-Finn C., Fennell D.A., Holmes S., Kerr K.M., Nakas A., Peel T., Rahman N.M., Slade M., Steele J., Tsim S., Maskell N.A. British Thoracic Society Guideline for the investigation and management of malignant pleural mesothelioma. Thorax. 2018; 73 (Suppl. 1): i1–i30. DOI: 10.1136/thoraxjnl-2017-211321.

Current population of patients with asthma is characterized by increasing resistance to standard pharmacotherapeutic agents such as inhaled corticosteroids, antileukotriene agents and anti-IgE antibodies. These findings were confirmed by international statistic data and indicate insufficient efficacy of the treatment. Asthma phenotyping encompassing a role of certain biomarkers for bronchial inflammation could contribute to achieving better response to treatment. Genetically engineered drugs could directly impact on mediators and modulators involved in the inflammation and bronchoconstriction. This is one of the most promising directions of the modern pharmacotherapy, particularly considering severe and difficult-to-treat asthma. A comparative analysis of efficacy and safety of currently available genetically engineered drug groups (monoclonal anti-IgE antibodies, monoclonal antibodies against interleukin (IL)-4/IL-13 and IL-5, and prostaglandin D2 receptor antagonists) was performed by the authors of this article on the basis of results of randomized controlled clinical trials (RCT). According to RCT results, omalizumab is still the leading genetically engineered drug. Moreover, evidence of efficacy and safety of novel agents has been published that allowed implementation these drugs in the routine clinical practice for treatment of severe eosinophilic asthma.

Combinations of inhaled corticosteroids (ICS) and long-acting bronchodilators are recommended for those patients with chronic obstructive pulmonary disease (COPD) who did not improve significantly with regular long-acting bronchodilators. ICS are known to increase the risk of pneumonia in elderly patients (over 55 years), current smokers, patients with acute exacerbation of COPD, patients with history of previous pneumonia, patients with body mass index < 25 kg/m2, and patients with dyspnea or severe airflow limitation. The risk-benefit ratio should be considered before initiating the treatment with ICS in COPD patients, particularly in patients with the risk factors of adverse events associated with ICS.

Cardiorenal relationships in patients with chronic obstructive pulmonary disease (COPD) are discussed in this review. Pathophysiology of cardiorenal syndrome is not fully understood, but supposed to be a complex condition resulted from neurohumoral activation, endothelial dysfunction, proteinuria, oxidative stress, uremia, and other factors. The airflow limitation in COPD could enhance those mechanisms. Recent studies discussed such therapeutic strategies as therapy of haemodymanic or neurohumoral abnormalities, but therapeutic approaches in this disease need further investigations. The lungs could play a role as a part of the cardiorenopulmonary syndrome. Effects of vitamin D on the main parameters of the cardiorenal syndrome and on COPD course have been published. Recent clinical and experimental findings consider vitamin D not only as a marker of the cardiorenal syndrome, but also as a therapeutic target in COPD.

Inhaled corticosteroids are widely used for the treatment of chronic obstructive pulmonary disease (COPD), but their efficacy significantly varies between patients. The aim of the study was to establish approaches to reveal steroid-sensitive and steroid-resistant patients with COPD using the blood and lung cells. Methods. Forty five patients with COPD undergoing bronchoscopy were recruited for the study of cytokine secretion by alveolar macrophages under the influence of glucocorticoids. Alveolar macrophages isolated from bronchoalveolar lavage fluid were cultured with lipopolysaccharide (LPS) and different concentrations of dexamethasone (0.01 – 1000 nM) for 24 h. Then, supernatants were removed and analyzed for concentrations of interleukin 6 (IL-6), IL-8 and tumor necrosis factor α (TNF-α). Binding of the glucocorticoid with its receptors was investigated in 24 patients with COPD, 20 healthy smokers and 20 healthy non-smokers. Blood cells were cultured with fluorescein isothiocyanate (FITC)-labelled dexamethasone and monoclonal antibodies against surface antigens of lymphocyte and monocyte populations. Fluorescence intensity of FITC-labelled dexamethasone was analyzed in blood cells using flow cytometry. Results. Dexamethasone significantly inhibited IL-6, IL-8, and TNF-α production in alveolar macrophages in a dose dependent manner. The maximal inhibition of cytokine production was observed at dexamethasone concentration of 100 nM, and the maximal cell response variability was found at 10 nM. IL-8 was less sensitive to the corticosteroid compared to IL-6 and TNF-α. Dexamethasone at any concentration failed to reach >50% inhibition of LPS-induced production of IL-8, IL-6 and TNF-α in alveolar macrophages of 40.0%; 11.1% and 8.9% of COPD patients, respectively. The fluorescence intensity of FITC-labelled dexamethasone in blood lymphocytes and monocytes was lower in smokers with COPD compared to healthy smokers and healthy non-smokers. The binding of dexamethasone with its receptors in the blood cells was higher in healthy non-smokers compared to healthy smokers. Conclusion. In vitro response of alveolar macrophages to glucocorticoids in COPD patients is characterized by significant inter-individual variability. The weak corticosteroid-related inhibition of IL-8 production can contribute to neutrophilic inflammation in COPD. The capacity of glucocorticoid receptors to bind with their ligands in blood lymphocytes and monocytes is decreased in COPD patients.

The aim of this study was to evaluate intracardiac hemodynamic abnormalities in patients with pulmonary sarcoidosis and to investigate relevant factors. Methods. The study involved 42 patients with chronic pulmonary sarcoidosis. Chest computed tomography (CT), echocardiography, body plethysmography, spirometry, 6-minute walking test, and measurements of lung diffusing capacity (DL_CO), blood gases and blood C-reactive protein (CRP) were performed in all patients. Results. Chronic cor pulmonale was detected in 26.2% of patients. The right heart diastolic dysfunction was found in 14.3% of patients, the left heart diastolic dysfunction was found in 23.8% of patients, the mean pulmonary artery pressure (mPAP) was increased in 19% of patients. The right ventricular diameter was found to be related to the inspiratory bronchial resistance (Rin) (R = 0.480; p = 0.02), the intrathoracic gas volume (ITGV) (R = –0.670; p = 0.001), DL_CO (R = 0.438; p = 0.013), and pulmonary fibrosis. The right heart systolic function (TAPSE) was related to DL_CO (R = 0.518; p = 0.006), the total lung capacity (TLC) (R = 0.639; p = 0.001) and pulmonary fibrosis. The increased mPAP was related to the extension of disseminated lung lesions (R = 0.716; p = 0.018), blood oxygen partial pressure (R = 0.486; p = 0.017) and CRP level. The 6-min distance was related to Rin, the right ventricular diameter, parameters of the right heart diastolic function (tricuspid E / A ratio) (R = 0.486; p = 0.01), and ITGV (R = 0.494; p = 0.006). Conclusion. The development of cor pulmonale in patients with pulmonary sarcoidosis was related to DL_CO, Rin and pulmonary fibrosis. The extension of disseminated lung lesions, hypoxemia and increased CRP were related to pulmonary hypertension. Different factors associated with cor pulmonale and pulmonary hypertension in sarcoidosis could prompt further investigation of different phenotypes of this disease with the intrinsic central hemodynamic abnormalities.

The aim of this study was to assess effects of antiinflammatory therapy with leukotriene receptor antagonists (LTA) and/or combination of an inhaled corticosteroid (ICS) and a long-acting β2-agonist (LABA) on the clinical course and airway inflammatory patterns in patients with severe asthma and cold air-provoked bronchial hyperresponsiveness. Methods. Asthma symptoms, lung function, and spontaneous sputum cytology were assessed at baseline and after 24 weeks of the therapy. Subgroup analysis was performed for patients with sputum eosinophils < 61% and sputum neutrophils < 61%. Eosinophilic patients were treated with fluticasone propionate/salmeterol, neutrophilic patients with treated with fluticasone propionate/salmeterol plus montelukast during 24 weeks. The control of the disease was assessed using Asthma Control Test (ACT). Results. After 24-wk treatment, eosinophilic patients improves asthma control from 10.9 ± 0.5 to 19.6 ± 1.3 according to ACT questionnaire (р < 0.001), FEV1 improved from 45.9 ± 3.7% pred. to 79.2 ± 2.2% pred. (р < 0.001). Sputum eosinophil number decreased from 27.9 ± 2.1% to 7.1 ± 1.9% (р < 0.001); sputum neutrophil number decreased from 21.1 ± 2.1% to 8.7 ± 2.3% (р < 0.001). In neutrophilic patients, ACT score improved from 8.9 ± 0.6 to 15.9 ± 1.2 (р < 0.001), FEV1 improved from 42.9 ± 2.6% pred. to 72.3 ± 2.5% pred. (р < 0.001). Sputum neutrophil number decreased from 76.8 ± 3.7 to 52.2 ± 4.3 % (р < 0.001); Sputum eosinophil number decreased from 8.1 ± 0.7% to 6.2 ± 0.4% (р < 0.05). After 24 weeks of the treatment, partial control of asthma (ACT 20 -24) was achieved in 63% and 29% of patients in eosinophilic and neutrophilic groups, respectively (χ2 = 1.81; р > 0.05) after treatment. Conclusion. Adding montelukast to the combined therapy with fluticasone propionate/salmeterol in patients with severe asthma, cold air-provoked bronchial hyperresponsiveness and increased sputum neutrophils did not resulted in better control of the disease. The analysis of airway inflammatory pattern could be used as an additional marker to predict treatment efficiency.

Idiopathic pulmonary fibrosis (IPF) is the commonest form of idiopathic interstitial pneumonias with very poor prognosis. Currently, diagnostic and treatment approaches to this disease have been revised. Confirmation of the diagnosis requires careful exclusion of other known causes of interstitial lung diseases and the presence of usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography (HRTC) and/or on lung biopsy. Also, multidisciplinary discussion involving experts with experience in the diagnosis of interstitial lung diseases is recommended. Given recent knowledge on pathogenesis of IPF antifibrotic drugs are recommended for the therapy of this disease. A clinical case that demonstrates the multidisciplinary approach to diagnosis of IPF is reported in this article.

Abnormal mobility of the posterior membranous wall of the trachea and large bronchi is seen in many bronchopulmonary chronic inflammatory diseases. Currently, clear explanation of a mechanism of the expiratory tracheal stenosis (ETS) is absent. The advanced ETS is associated with severe ventilation abnormalities including asphyxia and syncope. The latter conditions are considered as indications for surgical treatment. Results of the surgical treatment are controversial and are not fully acceptable. For this reason, the surgical treatment for ETS is not routinely used and any successive case of such treatment is of great interest. Strict indications, such as life-threatening conditions or failure of optimal medical treatment, are required for surgical treatment of patients with tracheomalacia and ETS. Surgical treatment for tracheomalacia and ETS is contraindicated in the case of lobar bronchial lesion impeding stabilization the membranous part of the tracheobronchial tree.