Characteristics of the Airway Microbiome of Cystic Fibrosis Patients.

Microbiota as an integral component of human body is actively investigated, including by massively parallel sequencing. However, microbiomes of lungs and sinuses have become the object of scientific attention only in the last decade. For patients with cystic fibrosis, monitoring the state of respiratory tract microorganisms is essential for maintaining lung function. Here, we studied the role of sinuses and polyps in the formation of respiratory tract microbiome. We identified Proteobacteria in the sinuses and samples from the lower respiratory tract (even in childhood). In some cases, they were accompanied by potentially dangerous basidiomycetes. The presence of polyps did not affect formation of the sinus microbiome. Proteobacteria are decisive in reducing the biodiversity of lung and sinus microbiomes, which correlated with the worsening of the lung function indicators. Soft mutations in the CFTR gene contribute to the formation of safer microbiome even in heterozygotes with class I mutations.

Spectrum of CFTR mutations in Chechen cystic fibrosis patients: high frequency of c.1545_1546delTA (p.Tyr515X; 1677delTA) and c.274G>A (p.Glu92Lys, E92K) mutations in North Caucasus.

BACKGROUND: Cystic fibrosis (CF; OMIM #219700) is a common autosomal recessive disease caused by pathogenic variants (henceforward mutations) in the cystic fibrosis transmembrane conductance regulator gene (CFTR). The spectrum and frequencies of CFTR mutations vary among different populations. Characterization of the specific distribution of CFTR mutations can be used to optimize genetic counseling, foster reproductive choices, and facilitate the introduction of mutation-specific therapies. Chechens are a distinct Caucasian ethnic group of the Nakh peoples that originated from the North Caucasus. Chechens are one of the oldest ethnic groups in the Caucasus, the sixth largest ethnic group in the Russian Federation (RF), and constitute the majority population of the Chechen Republic (Chechnya). The spectrum of CFTR mutations in a representative cohort of Chechen CF patients and healthy individuals was analyzed. METHODS: Molecular genetic analysis of 34 CFTR mutations (representing approx. 80-85% of mutations in multiethnic CF populations of the RF) was performed in 32 CF patients from 31 unrelated Chechen families living in Chechnya. One hundred randomly chosen healthy Chechens were analyzed for the 15 most common "Russian" mutations. The clinical symptoms in Chechen CF patients with different CFTR genotypes were investigated. RESULTS: High frequencies of c.1545_1546delTA (p.Tyr515X; 1677delTA) (52 out of 64 CFTR alleles tested; 81.3%) and c.274G > A (p.Glu92Lys, E92K) (8/64, 12.5%) mutations were found. Twenty patients were homozygous for the c.1545_1546delTA mutation, and eight were compound heterozygous for the c.1545_1546delTA and c.274G > A mutations. Three carriers of the c.1545_1546delTA mutation were also found in the cohort of 100 apparently healthy Chechens (frequency - 0.015). The c.1545_1546delTA and c.274G > A mutations are linked to the same haplotype (22-7-16-13) of intragenic Short Tandem Repeat markers, i.e., IVS1CA, IVS6aGATT, IVS8CA, and IVS17bCA. CONCLUSIONS: The distribution of CFTR mutations in the Chechen CF population is unique regarding the high frequency of mutations c.1545_1546delTA and c.274G > A (more than 90% of the mutant alleles). The c.274G > A mutation is associated with a less severe course of CF than that observed in c.1545_1546delTA homozygotes. Testing for these two variants can be proposed as the first step of CF DNA diagnosis in the Chechen population.

[Late diagnosis of celiac disease in a child with cystic fibrosis].

Cystic fibrosis is frequent monogenic disorder inherited in an autosomal recessive manner and has a severe course and prognosis. Crucial for the patient's life are the nature and extent of lung injury, as well as the digestive system, especially the pancreas and liver. Since the late 1960's. appeared describing a combination of celiac disease and cystic fibrosis. Many authors believe their associated diseases. Cited the case of late diagnosis of celiac disease in patient with cystic fibrosis, diagnosed as late, which delayed the appointment of adequate therapy, severe violations of nutritional status and physical development of the child, the current weighting of the underlying disease.

[Zinc and copper blood plasma and erythrocyte value in adolescent with the different types of pathology].

Comparative analysis the value of the cation of zinc and copper in the blood plasma and erythrocytes were performed in the different diseases in children and adolescent. The patients with bronchopulmonary diseases, liver diseases, low cardiovascular malformation and growth inhibition were examined. Increase the value of the intracellular zinc and copper was detected in patients with the definite bronchopulmonary diseases, which can on the one hand, reflected the activation of the antioxidant protection system and by another hand, reflected destructive metalloproteinase. Decrease the value of the intracellular copper in bronchopulmonary patients with the lung emphysema and Kartagnera syndrome indicate about the falure of the compensatory reactions and needs the additional investigation. It was detected that copper content in the blood plasma and the copper accumulation in erythrocyte were decrease in patients with liver diseases in comparison with the health children. The increase of copper value in erythrocyte in children with low cardiovascular malformation was detected and need the additional investigation. In children with the growth inhibition was detected appreciable decrease the value of the free zinc and copper ions in erythrocytes and copper in the blood plasma, which can explained the physical developmental lagging.

[Outcomes of the long-term treatment with a novel mucolytic drug pulmozin in mucoviscidosis patients]. / Opyt dlitel'nogo primeneniia novogo mukoliticheskogo preparata "pul'mozim" u bol'nykh mukovistsidozom.

AIM: To study clinical effectiveness and safety of a new mucolytic drug pulmozim (Switzerland) adjuvant to basic therapy in mucoviscidosis patients of different age in Russia. MATERIAL AND METHODS: 15 patients with mucoviscidosis aged 5-36 years, functional lung capacity and FEV-1 at least 40% received pulmozim for 30 days. The drug was given in a single daily dose 2.5 mg in inhalations. The study included three stages: initial 14 days--discontinuation of all mucolytic drugs, 30-day course of pulmozim, 14-day follow-up without pulmozim and other mucolytics. RESULTS: Pulmozim in the above regimen was effective in patients with mixed and moderate mucoviscidosis. The drug facilitates respiration, improves sputum rheology, normalizes general condition of the patient, is simple for use, has good organoleptic properties. CONCLUSION: Pulmozim is an effective mucolytic drug in combined treatment of mucoviscidosis.

Inflammatory markers in cystic fibrosis patients with lung Pseudomonas aeruginosa infection.

Chronic endobronchial inflammation and bacterial infection are the main causes of morbidity and mortality in cystic fibrosis (CF), an autosomal recessive genetic disorder associated with improper function of chloride channels. Inflammation in CF lung is greatly amplified after Pseudomonas aeruginosa infection. In this study the relationship between P. aeruginosa status and inflammatory markers has been investigated. Seventeen CF children in acute lung exacerbation were examined. CF patients without P. aeruginosa infection were characterized by elevated activity of sputum elastase, reduced response of peripheral blood lymphocytes to PHA and significant resistance to the antiproliferative action of glucocorticoids. These parameters were normalized after antibiotic treatment. The patients with prolonged P. aeruginosa infection demonstrated extremely high levels of elastase activity and elevated amounts of sputum IL-8 and TNF-alpha. Although antibiotic treatment resulted in clinical improvement, it failed to suppress excessive immune response in the lung. The data indicate that CF patients with prolonged P. aeruginosa need the modified treatment, which should include immunomodulating drugs and protease inhibitors as well as antibacterial therapy.

[Flutter therapy in the combined rehabilitation of children with mucoviscidosis]. / Flatter-terapiia v kompleksnoi reabilitatsii detei, bol'nykh mukovistsidozom.

Flutter proved to be a highly effective individual device able to considerably improve drainage function of the lungs. This increases therapeutic effect of combined therapy and therefore should be included in the program of rehabilitation of chronic lung disease patients, especially in mucoviscidosis. This method of kinesitherapy is aimed at both treatment of exacerbations of bronchopulmonary diseases and at their prevention.

[Use ciprofloxacin in children with mucoviscidosis]. / Opyt primeneniia tsiprofloksatsina u detei, bol'nykh mukovistsidozom.

Ciprofloxacin was used in treatment of 13 children aged 6 to 18 years with mucoviscidosis and exacerbation of the bronchopulmonary process. The dose of the drug was 20 to 30 mg/kg a day when administered orally or 15 mg/kg a day when administered at first intravenously and then orally. The treatment course averaged 14 days. The indications to the drug use were: severe processes of mucoviscidosis and chronic colonization of the bronchial mucosa and lung tissues with Pseudomonas aeruginosa (mucoid or nonmucoid form) sensitive to ciprofloxacin and resistant to other antibiotics. The trials showed that ciprofloxacin was highly efficient: the state of the patients improved and the inflammation index of the total blood count normalized. However, eradication of P. aeruginosa from the respiratory tracts was not observed. The drug allergy in 1 patient and a transient increase in the level of transaminases in 5 patients as the adverse reactions were recorded.

[Erythrophagocytic histiocytosis syndrome in a child with a primary immunodeficit]. / Sindrom éritrofagotsitarnogo gistotsitoza u rebenka s pervichnym immunodefitsitom.

The authors described a case of the syndrome of erythrophagocytic histiocytosis in an infant with primary immune deficiency who died at the age of 11 months and 20 days. Microscopic examination revealed focal and diffuse histiocyte proliferation in the bone marrow, lymph nodes, liver, and lung. Histiocytes were found to actively phagocytize erythrocytes and hemosiderin. The changes in the thymus were regarded as congenital primary unclassifiable immunodeficiency. The differential diagnosis of the syndrome was made in comparison with histiocytosis, histiocytosis X and familial erythrophagocytic lymphohistiocytosis.