BackgroundCystic fibrosis (CF) is one of the most common life-threatening genetic disorders. Around 2000 variants in the CFTR gene have been identified, with some proportion known to be pathogenic and 300 disease-causing mutations have been characterized in detail by CFTR2 database, which complicates its analysis with conventional methods.MethodsWe conducted next-generation sequencing (NGS) in a cohort of 89 adult patients negative for p.Phe508del homozygosity. Complete clinical and demographic information were available for 84 patients.ResultsBy combining MLPA with NGS, we identified disease-causing alleles in all the CF patients. Importantly, in 10% of cases, standard bioinformatics pipelines were inefficient in identifying causative mutations. Class IV-V mutations were observed in 38 (45%) cases, predominantly ones with pancreatic sufficient CF disease; rest of the patients had Class I-III mutations. Diabetes was seen only in patients homozygous for class I-III mutations. We found that 12% of the patients were heterozygous for more than two pathogenic CFTR mutations. Two patients were observed with p.[Arg1070Gln, Ser466*] complex allele which was associated with milder pulmonary obstructions (FVC 107 and 109% versus 67%, CI 95%: 63-72%; FEV 90 and 111% versus 47%, CI 95%: 37-48%). For the first time p.[Phe508del, Leu467Phe] complex allele was reported, observed in four patients (5%).ConclusionNGS can be a more information-gaining technology compared to standard methods. Combined with its equivalent diagnostic performance, it can therefore be implemented in the clinical practice, although careful validation is still required.Electronic supplementary materialThe online version of this article (10.1186/s12920-018-0328-z) contains supplementary material, which is available to authorized users.

One of the methods to evaluate lung function is body plethysmography. Body plethysmography allows to measure indicators that cannot be obtained during spirometry, that is: total lung capacity (TLC), bronchial resistance (Raw), and functional residual capacity (FRC). FRC measured by body plethysmography reflects thoracic gas volume (TGV or VTG), and includes both ventilated and poorly ventilated volume. Plethysmographic measurements are based on the principle of the relationship between pressure and volume at constant temperature and fixed amount of gas. This principle states that the absolute pressure exerted by a given mass of an ideal gas is inversely proportional to the volume it occupies if the temperature and amount of gas remain unchanged within a closed system (Boyle-Mariotte Law). In body plethysmography, the following parameters: TGV, vital capacity (VC), expiratory reserve volume (ERV), tidal volume (TV), inspiratory reserve volume (IRV), inspiratory capacity (IC), Raw are obtained. TLC, residual volume (RV) and its share in total lung capacity can be calculated. Reduced TLC allows to diagnose restrictive disorders of pulmonary ventilation. The RV and its share in TLC increase together with airway obstruction indicates air trapping. The TGV increase together with airway obstruction indicates hyperinflation. In the analysis of lung volumes predictive values, which are calculated by the formulas recommended by ATS/ERS statement, are used. The results are expressed as a percentage of the predicted value. Thus, body plethysmography is an important addition to spirometry and image methods of research, allowing to assess the functional state of the lungs more objectively; it helps to conduct the differential diagnosis and control the course of the disease.

The aim was to evaluate the ventilation inhomogeneity (VIH) by the multiple-breath nitrogen washout test (MBNW) after COVID-19 and to identify the relationship of the lung clearance index (LCI) with other functional parameters of the respiratory system. Methods. The cross-sectional study included 35 patients (97% men); the median age was 44 years. Spirometry, body plethysmography, diffusing capacity of the lung for carbon monoxide (DLco), MBNW test, and impulse oscillometry were performed. Dyspnea was evaluated by mMRC scale. MBNW test was performed using the Easy-one Pro, MBW Module (ndd Medizintechnik AG, Switzerland). Results. The patients were divided into 2 groups. Group 1 included 21 (60%) patients who were not diagnosed with VIH. Group 2 included 14 (40%) patients with VIH. The median testing period was 72 (47 - 109) days from the onset of COVID-19. The median of the maximum volume of lung damage determined by high-resolution computed tomography (CTmax) was 50% in the acute period of the disease and 12% during the study. The medians of all analyzed parameters remained normal in the study cohort as well as in groups 1 and 2, except the resonance frequency (fres) in group 2. Statistically significant differences were found between groups 1 and 2 in the absolute frequency dependence of resistance (R5 - R20), reactance area (AX), fres. Significant differences were also found in pathological changes of vital capacity, forced expiratory volume in the first second (FEV1), (R5 - R20). The abnormalities were more common in group 2. A significant correlation was shown between LCI with the ratio of residual lung volume to total lung capacity, (R5 - R20), AX, fres, relative frequency dependence of resistance, CTmax, FEV1 and trasfer-factor (DLco). Conclusion. Seventy-two days after the onset of CoVID-19, the ventilation inhomogeneity was detected in 40% of the patients, decreased DLco - in 23%, airway obstruction - in 11.4%, and restrictive ventilatory defect - in 8.6%. Correlations were found between LCI and DLco, spirometry parameters, body plethysmography, impulse oscillometry, and CTmax.

Over the past decades, the world has seen an increase in occupational lung diseases, the leaders being asthma and chronic obstructive pulmonary disease (COPD). The article presents the results of 5-year observation of food industry workers. Clinical functional and molecular genetic studies have been carried out to identify the frequency and severity of asthma and COPD along with the individual predisposition to pulmonary conditions.Methods. 76 people of both sexes with the average age of 43.5 ± 3.6 years were examined on an outpatient basis. All subjects had daily contact with toxic and allergenic aerosols and organo-mineral dust. The respiratory function and the presence of bronchial hyperresponsiveness to occupational factors was assessed by spirography and peak flowmetry in response to exposure and elimination of industrial aerosols. Immunological and molecular genetic tests were performed: identification of hyposecretory alleles of the α1 -АТ gene, determination of polymorphisms of the GSTM1 and GSTT1 genes, immunoglobulin levels (IgE, IgM, IgG) and cytokine status (IL-4, -6, -8; TNF-α).Results. During the 5-year follow-up period, there was a significant increase in the number of employees with severe respiratory symptoms – 36.8% (95% CI – 21.2–36.8; p < 0.05) and a statistically significant decrease in the respiratory function (p < 0.001). Progressive decrease in the respiratory function in healthy individuals and the appearance of new and more severe cases of asthma and COPD were registered primarily among workers with hyposecretory alleles of the α1 -АТ gene and/or zero alleles of the glutathioneS-transferase genes (GSTM1 and GSTT1) in combination with abnormal cytokine status.Conclusion. Individual risk factors for the development of asthma and COPD in individuals working in contact with toxic and allergenic aerosols and organo-mineral dust are hyposecretory PiMZ variant of the α1 -АТ gene and deletions in the glutathione-S-transferase genes (GSTM1 0/0 and GSTT1 0/0) in combination with abnormal cytokine status. Long-term research results suggest the prognostic value of assessing individual sensitivity to industrial aerosols and the development of bronchopulmonary pathology.

The article discusses the diagnostic and pathophysiological aspects of the study of the lungs diffusion capacity.