Bronchiectasis, ICD-10 – J47, (BE) is a chronic respiratory disease characterized clinically by cough, sputum production and bronchial infection, and radiographically by abnormal and persistent dilation of the bronchi. Common causes include cystic fibrosis, primary ciliary dyskinesia, immune disorders, systemic inflammatory diseases and infections, and other factors. However, some cases are idiopathic, when the cause cannot be identified. In practice, patients with bronchiectasis are divided into two groups: associated and not associated with cystic fibrosis. The prevalence of the disease varies significantly worldwide; it is not reliably known in the Russian Federation.The aim of the review is to analyze the literature data on modern approaches to the diagnosis of BE and to familiarize readers with diagnostic methods and basic approaches to the treatment.Methods. Data from 77 articles and the expert opinion of specialists providing care to patients with BE were used.Results. The main causes, frequency of occurrence, clinical phenotypes and treatment approaches for BE are described. There are many clinical, laboratory, instrumental and radiological features that provide insight into the etiology of BE. The European consensus is that the goal of treating BE is to restore or maintain normal lung function. There are no randomized trials on the treatment of BE, so all treatment guidelines are based on very low-level evidence or extrapolated from cystic fibrosis guidelines. Recommendations for mucolytic, antibacterial and anti-inflammatory therapy for BE are described, taking into account international and national experience.Conclusion. The development of a new version of clinical guidelines with modern relevant information will improve the diagnosis and treatment of BE in the Russian Federation.

This text is a continuation of a review of international studies and guidelines/recommendations for primary prevention of cystic fibrosis (CF). This section reviews the selection of pathogenic variants for different CF mutation carrier screening programmes to form panels, taking into account the geographical and ethnic characteristics of the couples being screened, describes the monitoring of couples at intermediate risk of carrier, presents the relationship between carrier screening and neonatal screening, highlights the importance of timely information, including medical and genetic counselling for stakeholders, taking into account the psychosocial status. Separately, we present studies that have found a reduction in the rate of CF births in France, Italy and Israel after the introduction of CF carrier screening.

Primary ciliary dyskinesia (PCD) is a rare genetic autosomal recessive disease associated with a defect in the ultrastructure of epithelial cilia. Currently, there is no standard method for diagnosing PCD, so the diagnosis is based on the clinical picture and the results of tests, such as DNA diagnostics, nasal nitric oxide measurements, ciliary beat frequency in a nasal biopsy, ciliary ultrastructure, etc. Diagnosis of PCD can be difficult due to secondary damage to the respiratory epithelium, which often results in undiagnosed or false positive cases. Differential diagnosis with diseases forming widespread bronchiectasis (BE) and upper respiratory tract lesions, especially with cystic fibrosis (CF), is necessary. The aim of this paper is to introduce the difficulties of diagnosis, the appropriate level of detail of the clinical, laboratory and instrumental characteristics over a long period of time, and the organization of care for a patient with PCD. This article describes a clinical case of PCD in a young woman, diagnosed at the age of 17, presents the difficulties and typical mistakes in the management of such patients, and the lack of succession of pediatrician-pulmonologist care. Conclusion. The presented clinical case demonstrates how difficult the diagnosis of PCD is. Such patients need a complex examination, a thorough differential diagnosis to exclude other diseases with a similar clinical picture. Long-term follow-up is carried out by a multidisciplinary team with mandatory microbiological monitoring. The organized care for patients should begin in early childhood and continue in adulthood with proper succession of care and follow-up by of pulmonologist, preferably in specialized centers.

In recent years, an increase in the number of patients with chronic infection with nonfermenting gram-negative bacteria (NFGNB) in adult patients with cystic fibrosis (CF) has increased. The genotype and phenotype characteristics, NFGNB structure, changes in sensitivity and the development of antibiotic resistance in adult patients have not been adequately studied. Aim. To determine the impact of genotype severity and Achromobacter xylosoxidans sensitivity to carbapenems on the functional and nutritional status of adult cystic fibrosis patients over a period 2016 – 2021. Materials. Retrospective analysis of genotypic and microbiological data from 54 adult CF patients and their effects on FEV1 and BMI over a period 2016 – 2021. Sputum cultures were confirmed by MALDI-TOF mass spectrometer. Depending on the severity of the mutation, the patients were divided into 2 groups: group 1 (“severe” genotype) – patients who had 2 mutations of class I – III; group 2 (“soft” genotype) – at least 1 class IV – VI mutation. Results. The group of patients with “mild” mutations had a higher BMI (kg / m2) than the group with severe mutations for a longer period of follow-up from 2018 – 2021 than in the group with severe mutations: BMI (2016) – 21.14 ± 3.55 / 19.28 ± 3.13 (p = 0.163); BMI (2017) – 21.27 ± 3.43 / 18.31 ± 2.05 (p = 0.123); BMI (2018) – 21.17 ± 4.00 / 18.80 ± 2.12 (p = 0.025); BMI (2019) – 21.01 ± 4.20 / 18.55 ± 2.53 (p = 0.049); BMI (2020) – 20.94 ± 4.12 / 18.41 ± 2.15 (p = 0.050). Age at diagnosis was 20.36 ± 2.18 years for “mild” genotypes and was higher (p = 0.042) than for “severe” genotypes (6.27 ± 1.53 years). All 7 patients who died (100%) were in the “severe” genotype group (23.3%). Functional status assessment showed no differences in FEV1 over 6 years between the “severe” and “mild” genotype groups: FEV1 (2016) – p = 0.51; FEV1 (2017) – p = 0.39; FEV1 (2018) – p = 0.51; FEV1 (2019) – p = 0.35; FEV1 (2020) – p = 0.48. Nonfermenting Gram-negative bacteria accounted for 49.9% of the isolated microorganisms. The group of carbapenem-resistant Achromobacter xylosoxidans lost the FEV1 level faster every year for 6 years (p < 0.05) compared to the group of the sensitive variant. Conclusion. In general, patients with the “mild” genotype have higher nutritional status and do not differ from patients with the “severe” genotype in terms of FEV1. The survival rate of patients with the “mild” genotype patients survival rate is higher, despite the later diagnosis and start of treatment. Development of carbаpenem resistance in Achromobacter xylosoxidans is associated with an unfavorable prognosis of the functional status decline.

Accepted, basic therapy of cystic fibrosis (CF), until recently, was symptomatic and aimed at slowing down pathological processes, mainly from the respiratory system and gastrointestinal tract, caused by a defect in the CFTR gene. New strategic opportunities have emerged since 2012 and are aimed at correcting a defect in a gene or its product. A mutation in the cystic fibrosis gene disrupts the function of the cystic fibrosis transmembrane conductance regulator protein (CFTR or CFTR in English transcription), which is located on the surface of the apical membrane of epithelial cells and functions as a chloride channel. The basic achievement for the new CF therapy was the discovery of small molecules that restore the processes of synthesis, transport to the membrane, or the functioning of the defective CFTR protein. The effectiveness of drugs that restore CFTR function is related to the ability of the molecules to deliver an adequate amount of the CFTR protein to the surface of the epithelial cell and/or improve its functional activity. Among them, correctors and potentiators for pharmacological modulation of ion transport are distinguished in clinical practice. Correctors are medicinal substances that allow the mutant CFTR protein to pass through the system of intracellular quality control and take the correct location on the apical membrane (with class II mutations). The action of potentiators is aimed at restoring (activating) the function of the ion channel formed by the mutant CFTR protein (class III–IV mutations). The purpose of this article is to analyze the literature sources, the results of clinical trials on the use of CFTR modulators, including combinations of a potentiator and a corrector. Their effectiveness and safety were evaluated. Literature sources (20) are used and own clinical observation is given. A positive assessment of the action of the modulator, the combination of a potentiator and a corrector, its safety and good tolerability is given. In conclusion, the place and indications for prescribing drugs of this class, the number of patients in the Russian Federation in need of such treatment are determined.

Primary ciliary dyskinesia (PCD) is a rare hereditary disease from the group of ciliopathies, which is based on a defect in the cilia ultrastructure of the respiratory epithelium and similar structures (sperm flagella, villi of the fallopian tubes, ventricular ependyma, etc.), leading to motor function impairment. The prevalence of the disease varies significantly around the world and is not known reliably in the Russian Federation.The aim of the review was to analyze literature data on modern approaches to the diagnosis and treatment of PCD.Methodology. The data of 90 articles and the opinions of experts providing care to patients with PCD were used.Results. The classic manifestations of PCD depend on age. The leading manifestations of the disease in patients with PCD are recurrent inflammatory diseases of the upper and lower respiratory tract (bronchitis, pneumonia), with the formation of bronchiectasis, damage to the ENT organs (chronic rhinitis, rhinosinusitis, nasal polyposis, repeated otitis media, progressive hearing loss). Currently, there is no single method which could serve as a “gold” standard for diagnosing PCD. The diagnosis of PCD is based on the characteristic clinical picture in combination with the results of special tests (nitric oxide in exhaled air, DNA diagnostics, high-speed video microscopy, transmission electron microscopy). The genetic diagnostics has not been developed sufficiently in the global practice yet and is unavailable in our country. The approach to the treatment of a patient with PCD should be multidisciplinary due to multiple organ lesions. According to the European consensus, the goal of PCD therapy is to restore or maintain normal lung function. There have been no randomized trials of treatment for PCD, and therefore all treatment recommendations are based on very low-level evidence or extrapolated from cystic fibrosis guidelines. Recommendations on mucolytic, antibacterial and anti-inflammatory therapy of PCD are given with consideration for the international and domestic experience.Conclusion. The development of a new version of clinical guidelines containing up-to-date relevant information will improve the diagnosis and treatment of PCD in the Russian Federation.

Aim: to evaluate the infection rate and resistance of isolated Achromobacter xylosoxidans to carbapenems in adult cystic fibrosis patients (CF). Patients and Methods: a retrospective analysis of the results of culture test and time-of-flight mass spectrometry MALDI-TOF was conducted: 685 sputum samples of 58 adult CF patients for a period of 5 years (2016–2020). To assess the sensitivity to imipenem and meropenem, the agar gradient diffusion and disk diffusion method were used. Results: the incidence of infection with A. xylosoxidans in adult CF patients for the period from 2016 to 2020 when monitoring a single sample of patients (n=24) to evaluate the occurrence of this pathogen with increasing age ranged from 16.6% in 2016–2017, increasing to 37.5% in 2018–2019, and with a further reduction to 20.8% (associated with disease fatal outcome in 3 of the 9 infected patients). There was no statistically significant dependence of the fatal outcome on infection with A. xylosoxidans. When analyzing the entire pool of patients (n=58) from 2016 to 2020, the release frequency of Pseudomonas aeruginosa remains approximately the same, varying from 63.3% to 46.5% and maintaining a numerical advantage in all follow-up periods, while the A. xylosoxidans infection ranges from 13.7% to 39.3%. In 2016–2018, 50% of isolates were sensitive to carbapenems, in 2018 — 53.8% of isolates, in 2019–2020 — the activity of obtained isolates decreased to 37.5% and 30.7%, respectively. Conclusion: despite the dynamics of indicators and the sample size, the dynamics over 5 years maintained a group-wide proportion of microbiome species dominated primarily by Pseudomonas infection and A. xylosoxidans. In our follow-up, the activity of carbapenems in relation to A. xylosoxidans has almost halved. KEYWORDS: cystic fibrosis, Burkholderia cepacia complex, Achromobacter xylosoxidans, Pseudomonas aeruginosa, lethality, antibiotic resistance, carbapenems. FOR CITATION: Makhmutova V.R., Gembitskaya T.E., Chermensky A.G. et al. Achromobacter xylosoxidans infection and resistance monitoring in adult cystic fibrosis patients. Russian Medical Inquiry. 2021;5(7):462–467 (in Russ.). DOI: 10.32364/2587-6821-2021-5-7-462-467.

The aim of the experts who provide health care for patients with cystic fibrosis (CF) has been to develop clinical guidelines on cystic fibrosis for children and adults. Methods. The 2020 Clinical Guidelines were based on the European consensus documents on cystic fibrosis and the national consensus “Cystic fibrosis: definition, diagnostic criteria, therapy” (2016, 2019). When creating clinical guidelines, the experts were guided by Article 2 of the Federal Law No.323-FL “On the basics of health care in the Russian Federation” as of November 21st, 2011, and the regulatory legal documents governing the development and approval of clinical guidelines (https://rosmedex.ru/kr/). Results. The clinical guidelines were approved by the Federal State Budgetary Institution “Centre for Expertise and Quality Control of Medical Care” of the Russian Ministry of Health in August 2020. Standards of medical care for children and adults with cystic fibrosis were prepared based on these guidelines. The diagnostic algorithms have been expanded with a three-stage DNA diagnostic strategy, functional assays of CFTR channel, laboratory and instrumental diagnostic tools for assessing disorders of respiratory and other systems, diagnosis of the microbial inflammatory process, microbiological monitoring, and therapeutic approaches. The antibiotic therapy with dosages and courses is described in detail. The updated document should describe a unified tactic for the management of Russian CF patients. Conclusion. Unified clinical guidelines for children and adults should develop unified tactics for the diagnosis, therapy, and follow-up of CF patients in the Russian Federation and ensure continuity between health care services for children and adults.

March 11, 2020 WHO has declared the COVID-19 coronavirus pandemic. The European Society for Cystic Fibrosis (ECFS) has developed the ECFSCOVID- 19 surveillance program to collect information on the characteristics of COVID-19 in patients with cystic fibrosis (CF). CF centers in the Russian Federation also joined the ECFS study. The ECFS collected information only through national Registers. In our country, the national register of CF patients has existed since 2011, its data is included in the European Register. Тo analyze the prevalence and course of COVID-19 in adult CF patients in Saint-Petersburg and the Leningrad region.Methods. From 11.03.20 to 24.12.20, 10 cases of adult CF patients (4 women, 6 men) with COVID-19 were analyzed in Saint-Petersburg and the Leningrad region. At the beginning of the study, 56 adult CF patients lived in Saint-Petersburg and Leningrad Region. All patients were monitored remotely by telephone, in case of ARVI symptoms, disease exacerbation, a PCR smear was performed on SARS-CoV-2, therapy was prescribed remotely, and inpatient treatment was prescribed if indicated.Results. COVID-19 was diagnosed in 10 adult CF patients aged 21 to 43 years. Two patients (32-year-old male and 31-year-old female with severe mixed cystic fibrosis form) were hospitalized with polysegmental pneumonia. 8 people were treated on an outpatient basis. Only 1 outpatient patient aged 43 years had pronounced clinical manifestations of COVID-19, the condition was regarded as moderate, the remaining outpatient patients suffered from a mild ARI disease. All patients were treated with positive dynamics. During the period of this follow – up, 3 CF patients (2 men, 1 woman) died, the death cause was the respiratory failure progression. Clinical and radiological, repeated laboratory data for COVID-19 were not obtained. At the point of December 24, 2020 53 adult CF patients are alive.Conclusion. According to our data, the incidence of COVID-19 among adult CF patients in Saint-Petersburg and the Leningrad Region was 17.85%, which is a lower indicator than in the general population. The disease was rarely severe, and effective treatment was noted in outpatient settings. There were no deaths from COVID-19.

Background: in Russia, the life expectancy of cystic fibrosis (CF) patients increased by 10 years in 2011–2017 being 55.49 years in 2017. However, the number of patients with the chronic infection caused by non-fermenting gram-negative bacilli (NFGNB), e.g., Burkholderia cepacia, Achromobacter spp. etc., increased as well. Aim: to evaluate the differences in the nutritional and functional status and the severity of mutations in CF patients with chronic Pseudomonas infection or NFGNB infection and to assess the sensitivity of P. aeruginosa to tobramycin in CF patients in the Northwest region of Russia. Patients and Methods: 31 patients with CF aged 18–43 years (18 men and 13 women) were examined. The duration of the study was 12 months. Spirometry, anthropometry, and sputum culture were performed. Results: P. aeruginosa alone was isolated in 18 patients (58%), Achromobacter spp. in 9 patients (29%), and Burkholderia spp. in 4 patients (13%). The patients were divided into two groups, i.e., patients with chronic Pseudomonas infection (group 1, n=18, 10 out of 18 patients with mucoid strains of P. aeruginosa) or chronic NFGNB infection (group 2, n=13). The median age and the mode age were 27 years and 27 years, respectively, in group 1 and 24 years and 22 years, respectively, in group 2. It was demonstrated that CF patients with chronic NFGNB infection are characterized by poorer nutritional status (p<0.05) but similar functional status and the severity of CFTR gene mutation compared to CF patients with chronic Pseudomonas infection. It was also shown that Р. aeruginosa is highly sensitive to tobramycin (94.4%). Conclusions: in CF patients, chronic lower respiratory tract infections with Burkholderia cepacia and Achromobacter spp. account for 41.9% of gram-negative rod infections. Further studies and drug sensitivity monitoring are needed. KEYWORDS: cystic fibrosis, DNA test, chronic infection with Pseudomonas aeruginosa, Burkholderia cepacia, Achromobacter spp, non-fermenting gram-negative bacilli, CFTR mutation, nutritional status, pulmonary function tests, inhaled antibiotic therapy. FOR CITATION: Makhmutova V.R., Gembitskaya T.E., Chermenskiy A.G. et al. Comparative characteristics and clinical presentation of cystic fibrosis in adults with chronic lower respiratory tract infections with Pseudomonas aeruginosa and other non-fermenting gram-negative bacilli. Russian Medical Inquiry. 2020;4(4):186–191. DOI: 10.32364/2587-6821-2020-4-4-186-191.

Детская клиническая больница № 1, ярославль 150003, Российская Федерация 36 Клиническая больница № 2, ярославль 150010, Российская Федерация Цель исследования.Изучить особенности и разнообразие спектра патогенных генетических вариантов гена CFTR (ABCC7) у российских пациентов с МВ, представленных в Регистре больных муковисцидозом (МВ) Российской Федерации (РФ) 2017г.Материал и методы.Проанализированы результаты генотипирования, включавшего анализ частых патогенных генетических вариантов, секвенирование кодирующей последовательности, поиск генных перестроек гена CFTR, 3096 больных из 81 региона-субъекта Российской Федерации, представленных в Регистре больных МВ в РФ 2017 г.Результаты.Выявлено 196 патогенных генетических вариантов гена CFTR.Суммарная доля 11 генетических вариантов c.1521_1523delCTT (F508del), c.54-5940_273+10250del21kb (CFTRdele2,3), c.274G>A (E92K), c.2012delT (2143delT), c.3718-2477C>T (3849+10kbC->T), c.3846G>A (W1282X), c.2052_2053insA (2184insA), c.1545_1546delTA (1677delTA), c.3909C>G (N1303K), c.1624G>T (G542X), c.413_415dupTAC (L138ins) составляет 75,6 %. 102 редких вариантов обнаружены однократно, 29 -дважды.Как в спектре, так и по частоте у пациентов в РФ преобладают варианты, приводящие к серьезным нарушениям функции белка CFTR (I, II, III классы).44 генетических варианта не внесены в базы CFTR1 и CFTR2.Заключение.На основании данных Регистра 2017 года определены спектр и относительные частоты патогенных вариантов последовательности гена CFTR у российских больных МВ; описано их распределение в зависимости от класса и типа.Выявлены генетические варианты, ранее не описанные в базах CFTR1 и CFTR2.Полученные результаты могут использоваться для оптимизации генетического консультирования и клинической работы с семьями, отягощенными МВ, а также для дальнейших исследований патогенетической значимости ранее не описанных генетических вариантов гена CFTR.

The article considers the incidence, mortality and in-hospital mortality rates from community-acquired pneumonia in St. Petersburg, 2009-2016. Epidemiological characteristics were studied in comparison with values in Russian Federation, as well as levels in Moscow and the Northwestern Federal District. The relationship between incidence and mortality rates from community-acquired pneumonia and epidemics of influenza was demonstrated. After the analysis of the medical records of patients who died of community-acquired pneumonia, defects in the organization of medical care, which had a negative prognostic impact, were indicated. A series of measures was proposed to improve the situation with community-acquired pneumonia in St. Petersburg.

Methods: The data of the register of patients with cystic fibrosis 2016 RF were analyzed.Comparison with the 2011 register is made.The study included 3049 patients, DNA diagnostics coverage amounted to 90.4%; 2011-1026 patients, DNA diagnostics -91.8%.Results: The allele frequency of the F508del mutation was 52.06% (61.51% in the ECFSPR 2015).In 2011 52.79%.In federal districts (FD), the lowest allelic frequency was in the North Caucasus FD (27%), the highest in the North-Western (57%), Southern (57%) and Siberian (56%) FD.The share of homozygotes for F508del decreased from 32.1% to 28.3% over 5 years, the number of heterozygotes increased from 41.2% in 2011 to 47.2% in 2016, the number of genotypes without F508del in 2011 was 26.7%, and in 2016-24.5%.The share of homozygotes for F508del varied from 11% in the North Caucasus FD to 33% in the Southern, Far Eastern and Siberian FD.The number of patients without the F508del mutation was the lowest in the Northern FD (15%), the Southern (19%), the highest in the North Caucasus FD (58%) and the Volga Region (29%).Among children the share of homozygotes for F508del was 29.8%, heterozygotes -46.1%, without F508del -24.0%, among adultshomozygotes for F508del-23.6%, heterozygotes-50.7%,without F508del-26.1%.The highest share of homozygous F508del was observed among children aged 8 to 12 years31.2%,the lowest in the age of 36 years 4.3%. Conclusion:The frequency of homozygotes for F508del remains unchanged from 2011, depending on age of the patients and the place of residence.The frequency of F508del homozygotes in the RF is 28.3% and lower than in Europemore than 40% submitted by the ECFSPR 2015.

The aim of this study was to investigate genetic features of patients with cystic fibrosis (CF) according to the National Register findings in Russia. Methods. The study involved 2,131 CF patients living in 74 regions of Russia who were included in the National Register of CF patients in 2014. Results . Genetic testing was performed in 89% of patients. The total mutant allele frequency was 81.2%. One hundred and twenty two mutations were found which comprised 173 genotypes; «mild» mutations took 23%. The most common mutant allele frequencies in the descending order were as follows: F508del, 51.53%; СFTRdele2,3, 5.93%; E92K, 2.62%; 3849+10kbC>T, 2.14%; 2184insA, 1.80%; W1282X, 1.80%; 2143delT, 1.69 %; N1303K, 1.43%; G542X, 1.16%; 1677delTA, 0.98%; L138ins, 0.95%; R334W, 0.85%; 394delTT, 0.85%; 3821delT, 0.42%; 2789+5G>A, 0.37%; S466X, 0.37%; S1196X, 0.37%; 3272-16T>A, 0.34%; W1282R, 0.29%; 3944delGT, 0.21%. Typical features of CFTR mutation distribution in Russian CF patients were lower frequency of mutations which are predominant worldwide, such as F508del, G542X, N1303K, and scarce G551D, 1717-1G>A, 2183AA>G mutations. On contrary, СFTRdele2,3, E92K, 2184insA, 2143delT, 1677delTA, L138ins mutations which are quite rare in Western Europe were encountered more often in Russia. «Mild» mutations were more common in Russian population of CF patients compared to European countries and have being increasing last years. Conclusion. Genetic features of Russian CF patients could be provided by Slavic, Turkic and Finno-Ugric genetic influence on Russian population.

Genotypic and phenotypic features of patients over 18 years of age with late-onset unclassical cystic fibrosis have been analyzed in this article. The patients had relatively mild disease without significant exocrine pancreatic insufficiency.

Genotypic and phenotypic features of patients over 18 years of age with late-onset unclassical cystic fibrosis have been analyzed in this article. The patients had relatively mild disease without significant exocrine pancreatic insufficiency.

The aim of this study was to evaluate clinical efficacy and safety of highly concentrated inhaled solution of tobramycin (Bramitob ® , Chiesi Farmaceutici S.p.A., Italy) in patients with cystic fibrosis (CF). This was 24-wk multicenter international double-blind placebo-controlled randomized trial in parallel groups. In this study, 247 patients aged 6–45 yrs with Pseudomonas aeruginosa yielded in sputum and FEV 1 40 % to 80 % pred. were randomized in 2 groups: those inhaling aerosol tobramycin (161 patients, mean age, 14.8 ± 5.7 yrs) or placebo (84 patients, mean age, 14.7 ± 6.6 yrs). Tobramycin 300 mg b.i.d. was given at the time of basic and antipseudomonal therapy. Efficacy criteria were as follows: lung ventilation parameters, sputum culture and yielding P. aeruginosa, rate of exacerbations of pulmonary disease, rate of hospitalisations, number of workoff or school-off days, number of courses of parenteral tobramycin and other antipseudomonal antibiotics, nutritional status (weight, BMI). Safety profile included serum creatinine level, audiometric test, vital signs (heart rate, blood pressure) and adverse events. To the end of the study, FEV1 improved by 7 % in the tobramycin group and by 1 % in the placebo group ( p < 0.001), FVC improved by 5.7 and 1.3 %, respectively ( p = 0.002), and FEF 25–75 improved by 8.8 % and 0.7 %, respectively ( p = 0.001). Frequency of P. aeruginosa eradication differed significantly between the groups to the end of 4th and 20th weeks of the study (30.8 % vs. 14.3 %; p = 0.011, and 33.3 % vs. 16.5 %; p = 0.024, respectively). Exacerbations of pulmonary disease occurred in 39.8 % of tobramycin patients and in 51.2 % of placebo patients ( р = 0.09). Hospital admission was required in 18.6 % and 36.9 % of patients, respectively (p = 0.002). Parenteral tobramycin was administered to 6.2 % and 16.7 % of patients, respectively ( p = 0.009), other antipseudomonals were given in 55.9 % and 70.2 % of the patients, respectively ( p = 0.029). Number of patients with missing work/school days due to exacerbation of pulmonary disease was 32.3 % in tobramycin group and 57.1 % in placebo group ( p < 0.001). Serious adverse events related to treatment with tobramycin were not noted. In conclusion, long-term intermittent treatment with inhaled solution of tobramycin additionally to basic and antipseudomonal therapy in CF patients significantly improved lung ventilation and eradication of P. aeruginosa, decreased the rate of exacerbations of pulmonary disease, rate of hospitalisations, and numbers of antipseudomonal courses and missing work days. The treatment was well tolerated and could be recommended for CF patients with P. aeruginosa in culture.

The ratio between the normal (+) and null (0) alleles of the genes encoding glutatione S-transferases M1 (GSTM1) and T1 (GSTT1) were studied in normal individuals from northwestern Russia (control group) and in patients with bronchial asthma (BA). The frequency of the GSTM1 0/0 genotype in the population sample was statistically significantly lower (37.8%) than in the BA patients (82.1%; χ2 = 16.8;P< 0.001; Wχ2 = 15.7; α = 0.01). For the GSTT1 gene, similar data were obtained. The frequency of the GSTT1 0/0 genotype in healthy donors was statistically significantly higher (16.3%) than in the BA patients (73.7%; χ2 = 28.5;P < 0.001; Wχ2 = 23.22; α = 0.01). A significant preponderance of the compound homozygotes for the GSTM1 and GSTT1 null alleles among the BA patients was observed. The frequency of the GSTM1 0/0, GSTT10/0 individuals among the patients was 57.9%, while it was only 4.7% among the controls (χ2 = 27.4; P < 0.001).