The aim of this study was to investigate phenotypic features of cystic fibrosis (CF) in patients carrying the complex allele S466X(TGA)-R1070Q. Methods. Data from CF register of Russian Federation, 2014, were used. The Russian CF register includes data of 2,131 patients from 74 regions of Russian Federation. The complex allele S466X(TGA)-R1070Q was found in 17 patients (the study group) and homozygous F508del mutation was found in 170 patients (the control group). The groups did not differ in main clinical, functional and microbiological parameters. Survival was also investigated. Results. Sweat chloride concentration was higher in the study group patients compared to the control group (116.53 mmol/L vs 102.2 mmol/L; р = 0.0341). There were 11.77% of deaths in a combined group of patients with the complex allele vs 3.53% in homozygous F508del mutation group (р = 0.159). Moreover, no significant difference in survival was found between the groups (p = 0.058). FEV1 was higher in the study group (84.69 ± 17.85%pred. vs 64.95 ± 27.16%pred. in the control group: р = 0.0483). Patients did not differ significantly in percentiles of height, weight, and body mass index. Amyloidosis and pneumothorax were seen in the control group, but not in patients with the complex allele S466X(TGA)-R1070Q. Polyps were diagnosed in 19 (11.17%) of patients with F508del/F508del genotype and were not found in the study group patients. Prevalence of diabetes mellitus and hepatic cirrhosis was similar in both the groups. Osteoporosis was diagnosed in 10% of control patients and in one (5.88%) of the study group patients. Chronic or intermitted Pseudomonas aeruginosa infection and chronic infection of Staphylococcus aureus were equally seen in both the groups, but Burkholderia cepacia сomplex and Stenotrophomonas maltophilia were found more often in the study group patients compared to controls (23.52% vs 10.58% and 11.76% vs 2.35%, respectively). Conclusion. The results of this study confirmed that the complex allele S466X(TGA)-R1070Q has properties of class I mutation and should be considered as a “severe” mutation.

The diagnosis of primary ciliary dyskinesia is often confirmed with standard, albeit complex and expensive, tests. In many cases, however, the diagnosis remains difficult despite the array of sophisticated diagnostic tests. There is no “gold standard” reference test. Hence, a Task Force supported by the European Respiratory Society has developed this guideline to provide evidence-based recommendations on diagnostic testing, especially in light of new developments in such tests, and the need for robust diagnoses of patients who might enter randomised controlled trials of treatments. The guideline is based on pre-defined questions relevant for clinical care, a systematic review of the literature, and assessment of the evidence using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. It focuses on clinical presentation, nasal nitric oxide, analysis of ciliary beat frequency and pattern by high-speed video-microscopy analysis, transmission electron microscopy, genotyping and immunofluorescence. It then used a modified Delphi survey to develop an algorithm for the use of diagnostic tests to definitively confirm and exclude the diagnosis of primary ciliary dyskinesia; and to provide advice when the diagnosis was not conclusive. Finally, this guideline proposes a set of quality criteria for future research on the validity of diagnostic methods for primary ciliary dyskinesia.

This article has supplementary material available from erj.ersjournals.com 

• Adopted from: Lucas J.S., Barbato A., Collins S.A., Goutaki M., Behan L., Caudri D., Dell Sh., Eber E., Escudier E., Hirst R.A., Hogg C., Jorissen M., Latzin Ph., Legendre M., Leigh M.W., Midulla F., Nielsen K.G., Omran H., Papon J.-F., Pohunek P., Redfern B., Rigau D., Rindlisbacher B., Santamaria F., Shoemark A., Snijders D., Tonia Th., Titieni A., Walker W.T., Werner C., Bush A., Kuehni C.E.. European Respiratory Society guidelines for the diagnosis of primary ciliary dyskinesia. Eur. Respir. J. 2017; 49 (1): 1601090. DOI: 10.1183/13993003.01090-2016.

Published studies on gender aspects of the natural course of asthma are controversial and do not give information on gender difference of asthma. However, most studies showed a gradual increase in prevalence of asthma symptoms and morbidity in girls. Gender difference in asthma course was shown in several studies. In patients older 40 years, asthma was confirmed in women significantly more often. Female gender was shown to be an independent risk factor of non-allergic asthma. Natural course of asthma in females was more severe than in males. Gender difference is also related to a rate of hospitalization due to asthma. Hospitalizations due to asthma and need in reliever medications are more often in boys younger 12 years and in girls after puberty. This tendency maintains in adults.

According to this review, one can conclude that gender difference in the natural course of asthma appears in puberty and could be explained by gender difference in anatomy of the airways and endocrine system that could lead to more prominent bronchial hyperreactivity and, as a result, worse asthma control.

Therapeutic options for idiopathic pulmonary fibrosis (IPF) have been significantly extended last decade due to clinical use of drugs with confirmed antifibrotic activity, nintedanib and pirfenidone. Results of completed randomized phase III clinical trials (RCT) showed the ability of these drugs to decrease IPF progression and all-cause mortality compared to placebo. No direct comparison of efficacy and safety of different pharmacotherapeutic regimens with nintedanib and pirfenidone in IPF patients was published. The pooled odds ratio for mortality was 0.70 (95% confidential interval (CI), 0.47–1.03) in three trials of nintedanib (INPULSIS-1, INPULSIS-2, and TOMORROW; 2015) and 0.70 (0.47–1.02) in three trials of pirfenidone (CAPACITY-1, CAPACITY-2, and ASCEND). RCTs evaluating clinical efficacy of nintedanib and pirfenidone were not designed to assessment of mortality as the primary end-point; the primary end-point in all the trials was the change in the forced vital capacity of the lungs. Published metaanalyses demonstrated similar effects of nintedanib and pirfenidone on all-cause mortality and mortality from respiratory causes and confirmed favourable effects of both the drugs on course and progression of IPF.

Pulmonary hypertension (PH) is a large group of diseases characterized by pulmonary artery pressure (PAP) > 25 mm Hg. Currently, specific medications are available for several groups of PH only. These are prostacyclin analogues, soluble guanylate cyclase (sGC) stimulators (sGCS), phosphodiesterase-5 inhibitors (iPDE-5), and endothelin receptor antagonists. Modern evidence-based pharmacological treatment of PH and therapeutic algorithm have been described in this review. Particular attention was paid to mechanisms of dysregulation of vascular tone including nitric oxide (NO-sGC-cGMP) pathway that is a target for sGCS and iPDE-5. A new class of sGCS principally differs from iPDE-5 and is very important for clinical practice. Safety, availability and benefit of switching from iPDE-5 to riociguat was investigated in the RESPITE trial. Results of main clinical trials of efficacy and safety of riociguat in patients with pulmonary arterial hypertension and thromboembolic PH were also discussed in this review.

This study was aimed at investigation of effects of vaccination against influenza and pneumococcal infection on seasonal morbidity and mortality of influenza, acute respiratory viral infections (ARVI) and community-acquired pneumonia (CAP) in 2012 – 2016 in population of the Central district of Moscow. Methods. Data for the analysis were obtained from official statistic reports and death certificates of patients died in a hospital from flu and CAP. Results of virological investigations of nasopharyngeal swabs for viral RNA of influenza А(H1N1)09v, А(H3N2), and В, and results of bacteriological investigations of sputum and were also used. Results. The morbidity of infectious and parasitic diseases in the Central district of Moscow has decreased by 21.0% in 2016, if compared to 2012, including 19.0% decrease for ARVI. Morbidity of flu increased, probably due to epidemic circulation of influenza virus and improvement in laboratory diagnosis. CAP morbidity was associated with epidemic circulation of influenza and other respiratory viruses and has increased from 2015 to 2016. The highest morbidity of CAP and severe fatal CAP were registered during influenza epidemics. There was a 1.95-fold increase in vaccination coverage against influenza and 3.69-fold increase in vaccination coverage against pneumococcal infection. Though CAP and influenza morbidity increased, vaccination was related to decrease in mortality from CAP in 2016. Conclusion. The results demonstrated that ARVI morbidity in the Central district of Moscow had decreased in 2012 – 2016, but influenza incidence increased. Pneumonia morbidity was associated with epidemic growth of flu and ARVI morbidity. Vaccination coverage against flu and CAP increased and resulted in decreased morbidity of ARVI and decreased mortality from CAP and influenza.

The aim of the study was to investigate clinical features of interstitial lung diseases (ILD) using data from the register of Irkutsk residents with ILD. Methods. Medical history, clinical and functional data and data of high-resolution computed tomography (HRCT) of the lungs of 110 patients (67 women, 43 men, mean age, 56.2 ± 15.9 years) were analyzed. Lung biopsy was performed in 49 patients (45%). Results. Bilateral slowly resolving and/or recurrent pneumonia, unexplained pulmonary dissemination and idiopathic pulmonary fibrosis were the most frequent referral diagnoses. After thorough examination, three groups of ILDs were diagnosed most often: ILD with a known cause (32%), idiopathic interstitial pneumonias (30%), and pulmonary sarcoidosis (29%). Cough and dyspnea were the leading symptoms at ILD onset (in 48% and 39% of patients, respectively). The average duration of respiratory symptoms was 29.5 ± 33.0 months. Asymptomatic radiological abnormalities were the only reason for diagnostic work-up in 13% of the patients. Conclusion. Diagnosis of ILD is quite challenging for primary care physicians and pulmonologists. Accuracy and timeliness of diagnosis of ILD requires multidisciplinary approach as far as depends on quality of diagnostic procedures including medical history, lung auscultation, lung function testing, HRCT, and morphological examination, but also on the physician’s awareness and clinical experience.

The aim of this study was to investigate a role of postprocessing techniques of multidetector computed tomography (CT) and virtual bronchoscopy for differentiation between inflammatory lung lesions and lung tumorous. Methods. Native multidetector CT images of 39 patients with confirmed lung inflammatory lesions and postprocessing reconstruction with virtual bronchoscopy technique were analyzed. 16-slice computed tomograph Toshiba Aquilion 16 and 320-slice computed tomograph Toshiba AquilionONE were used. Results. Focused investigation of bronchial macrostructure in abnormal areas allowed exclusion malignancy and confirmation the inflammatory origin of abnormalities. Conclusion. Virtual bronchoscopy is complementary to native multidetector CT. Key criteria of inflammatory lesions were visualization of air-filling bronchi in an abnormal area, preserved bronchial lumen notwithstanding possible mucus accumulation in the bronchi, the absence of bronchial blockage, and cavity drainage through the bronchus.

This study was aimed at measuring concentrations and investigation of relationships between macro- and microelements in mediastinal lymph nodes of patients with sarcoidosis. Methods. The study involved 28 patients (50% were males; median age, 42.5 (23; 53) years) with confirmed diagnosis of sarcoidosis. Autopsy samples from 13 individuals died from occasional causes (41.2% were males; median age, 43 (38.7; 61.3) years) were used for comparison. The groups did not differ in age and gender. Neutron activation analysis was used to investigate chemical elements in mediastinal lymph node tissue samples. Results. Concentrations of Ca, Cr, Fe, Co, Zn, Rb, Sb, Cs, Ba, Eu, Lu, Yb, Hf, Th, and U in the lymph node tissue of patients with sarcoidosis were increased, and concentration of zinc was decreased compared to control samples. Concentrations of Sm, Au, Sr, Nd, As, Br, Ag, Tb, Sc, Ta, Na, and La did not differ between the groups. Direct relationships were found in element groups Fe-Cr-Sb-Ca, Fe-U-Th, Co-U-Th, U-Cr, Th-Br, Sc-Zn, Eu-La, and Ce-Lu.

The aim of this study was to investigate functional status and typical symptoms in patients with chronic obstructive pulmonary disease (COPD) and atrial fibrillation (AF). Methods. Stable patients with moderate to very severe COPD (n = 94) with or without AF were involved in the study. Spirometry, 24-h monitoring of electrocardiogram and arterial pressure were done in all patients. COPD symptoms were assessed using Modified Medical Research Council Scale (mMRC) and COPD Assessment Test (CAT). We analyzed a rate of moderate and severe acute exacerbations of COPD during the previous year; parameters of 6-minute walk test (distance, pulse oximetry and dyspnea using Borg’s scale) and BODE index. Results. AF paroxysms were registered in 46 patients; AF was asymptomatic in 22 patients. Thereafter, COPD patients were divided into two clusters, with and without AF. Comparison of the two clusters showed that patients with COPD and AF had more severe bronchial obstruction (p < 0.001), more frequent acute exacerbations of COPD (р = 0.038), more severe COPD symptoms (CAT, р < 0.001; mMRC, р = 0.007) and higher BODE index (р < 0.001). Also, patients with COPD and AF had more severe hypoxemia (р = 0.012), more severe dyspnea evaluated with Borg’s scale (р < 0.001) and shorter distance in 6-minute walk test (р ˂ 0.001) compared to COPD patient without AF. Conclusion. Higher rate of acute exacerbations of COPD, prominent decrease both in FEV1 and in physical tolerance, higher BODE index and higher mMRC and CAT scores were typical for COPD patients with AF paroxysms.

This study was aimed at investigating pathogenesis of pulmonary vascular abnormalities in COPD with systemic features, and ways to treat these circulatory disorders. Methods. We analyzed pulmonary vascular parameters, molecular markers of endothelial dysfunction, pulmonary artery pressure (PAP) and gas exchange in patients with moderate (n = 64) and severe (n = 70) COPD treated with basic therapy with or without an endothelial protector. Results. The results showed that perfusion disorders could appear in different parts of the lungs, probably, due to different mechanisms of these abnormalities. Localization of perfusion disorders was related to blood levels of molecular markers of endothelial dysfunction: adhesion molecules sP-selectin and sVCAM-1 were related to perfusion abnormalities in the upper lobes, VEGF-A was related to perfusion abnormalities in the lower lobes, and diffuse perfusion abnormalities were related to endothelin-1. Additional treatment with sulodexide improved endothelial function and pulmonary circulation, decreased PAP and blood concentrations of molecular markers of endothelial dysfunction. Conclusion. Predominant localization of microcirculatory abnormalities in COPD patients, especially in the lower lobes, is related to ventilation abnormalities, could predict clinical course of the disease and indicates the need in endotheliotropic therapy.

This study was done to analyze respiratory mechanics and lung diffusing capacity in patients waiting for lobectomy or pneumonectomy in order to predict postoperative risk of cardiorespiratory complications, to choose the surgical treatment strategy and the optimal anesthesiologic approach. Methods. We analyzed parameters of spirometry, body plethysmography and diffusing capacity for carbon monoxide in 30 patients (86.7% were males; mean age, 66.6 ± 10.3 years) before lobectomy or pneumonectomy. Results. Ventilation abnormalities were found in 73.3% of the patients (obstructive abnormalities in 56.7%; restrictive abnormalities in 3.3%, and mixed abnormalities in 13.3%). Lung diffusing capacity (transfer-factor) was reduced in 33.3% of patients; this was accompanied by ventilation defects in 90% of cases. Given the lung tissue volume proposed for resection the expected postoperative forced expiratory volume in 1 second and transfer-factor were calculated. Thereafter, the patients were included in a group of low, moderate or high risk of postoperative complications according to the estimates, and to the ratio of the actual residual volume and the total lung capacity. Conclusion. The results could be used to choose the surgical treatment strategy and the optimal anesthesiologic approach.

The optimal choice of effective and safe mucolytic drug is an important issue, especially in pediatric practice. A role of N-acetylcysteine (NAC) for treatment of upper and lower respiratory infections in children has been discussed in this review. Randomised controlled trials confirmed significant mucolytic effect and safety of NAC in children > 2 years old without excessive increase in bronchorrhea. Compared to other mucolytics NAC has additional therapeutic properties such as antioxidant and antitoxic (particularly, in paracetamol poisoning). NAC could destroy bacterial biofilms and prevent their occurrence. Original NAC (Fluimucil®) is available in different drug formulations: granules and tablets for oral solution, solution for inhalation and parenteral use. Since 2016, Fluimucil has been available as oral solution for children ≥ 2 years old with ease dosing.