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.

[Enteral tube feeding in adult patients with cystic fibrosis and respiratory failure]. / Énteral'noe zondovoe pitanie u vzroslykh bol'nykh mukovistsidozom s dykhatel'noi nedostatochnost'iu.

AIM: To evaluate the efficiency of nocturnal hyperalimentation in adult patients with cystic fibrosis (CF) and respiratory failure. SUBJECTS AND METHODS: The investigation enrolled 17 patients older than 18 years (mean age, 25.6±4.2 years) diagnosed with very severe CF (forced expiratory volume in one second (FEV1), < 30%; body mass index (BMI), < 18.5 kg/m2); all the patients were on the waiting list for lung transplantation. Nutritional status and pulmonary function parameters, such as body weight, height, BMI, and FEV1, were measured at baseline, before and 6 and 9 months after tube feeding. RESULTS: The study group showed a considerable increase in body weight and BMI after 6 and 9 months. The change in lung function was statistically insignificant. Lung transplantation was successfully conducted in 5 patients; 4 died while on the waiting list; the cause of death was respiratory failure. CONCLUSION: Supplemental PEG tube feeding improves the nutritional status (BMI, body weight) of patients with very severe CF.

[Nutritional status in patients with cystic fibrosis: Possibilities of correction]. / Status pitaniia u bol'nykh mukovistsidozom: vozmozhnosti korrektsii.

The major risk factor for death in cystic fibrosis (CF) is a progressive lung injury; however, low nutritional status (NS) remains an important and underestimated problem in the management of these patients. The NS of a patient with CF is impaired by many factors, such as chronic malabsorption, pancreatic failure, chronic inflammation, and recurrent pulmonary infection - they all lead to higher energy demand in the presence of lower intake of nutrients. The NS of those with CF plays an important role in maintaining lung function. The patients with higher NS have longer life expectancies. According to the Russian National Registry, both pediatric and adult patients with CF have shorter life expectancies. The article discusses various nutritional support regimens and their impact on lung function parameters.

[ANTIBIOTICS SENSITIVITY OF STAPHYLOCOCCUS AUREUS, PSEUDOMONAS AERUGINOSA AND BACTERIA OF BURKHOLDERIA CEPACIA COMPLEX, PERSISTING IN LUNGS OF PATIENTS WITH MUCOVISCIDOSIS (MV)].

AIM: Study the spectrum of resistance to antibiotics and its variability of Staphylococcus aureus, Pseudomonas aeruginosa and Burkholderia cepacia complex (BCC), persisting in lungs of MV patients. MATERIALS AND METHODS: 312 strains of S. aureus, 213 strains of P. aeruginosa, 186 strains of BCC were studied. Monitoring of antibiotics sensitivity was carried out in strains, isolated from 30 patients with chronic S. aureus infection, from 22 patients with chronic BCC infection and from 21 patients with chronic pseudomonas infection. Interval of monitoring was from 14 days to 5 years 7 months. RESULTS: Study of S. aureus, P. aeruginosa and BCC strains has shown, that 35 and 33.3% of cases of staphylococcus infection, 37 and 46% of pseudomonas infection in children and adults, respectively, 100% of BCC infections were determined by multi-resistant clones. Study of genotypically identical strains, isolated from a single patient at different stages, has shown a change in antibiotics sensitivity as a result of persistence. CONCLUSION: Persisent infection of lungs in patients with MV is determined: by exchanging clones with varying antibiotics sensitivity or prolonged circulation of a single clone with a high degree of phenotypical and genotypical variability, that determine alteration of seeding of sensitive and resistant strains from the same patient during monitoring. This confirms the necessity of study of antibiotics sensitivity of strains for prescription of antibacterial therapy.

[Use of high-frequency chest wall oscillation in an exacerbation of chronic pyo-obstructive bronchitis in adult patients with cystic fibrosis].

AIM: To evaluate the efficiency of high-frequency chest wall oscillation in the treatment of an exacerbation of chronic pyo- obstructive bronchitis in adult patients with cystic fibrosis (CF). SUBJECTS AND METHODS: A simple open-label comparative study enrolled 31 patients with CF. C-reactive protein (CRP), spirometric indicators (forced vital capacity (FVC), forced expiratory volume in one second (FEV1), peak expiratory flow), hemoglobin oxygen saturation, anthropometric data, six-minute walk test, and dyspnea rating by the MRC scale were assessed before treatment and on the last day of hospitalization. All the patients received conventional drug therapy; the study group patients (n=15) had the latter in combination with vibration-compression therapy for 15 minutes twice daily at a vibration frequency of 9-12 Hz and at an amplitude of 6-9 bars; the treatment cycle lasted 12-14 days. RESULTS: Both groups showed significant changes in spirometric and pulsometric readings, 6-minute walk test results, and MRC score. Body mass index increased and CRP decreased in the majority of patients in both groups. There were significant group differences in functional and anthropometric changes: 10.0 ± 4.6 and 6.9 ± 3.6% for FEV1 (p = 0.04) and 9.5 ± 4.8 and 5.9 ± 3.8% for FVC (p = 0.03) in the study and control groups, respectively. CONCLUSION: Incorporation of vibration-compression therapy (Vest vibro drainage) into the combination treatment of adult patients with CF results in significantly improved bronchial patency and more effective abolishment of an exacerbation.

[Characterization of genotypes for Burkholderia cepacia complex strains isolated from patients in hospitals of Russian Federation].

88 cultures of microorganisms referred to the Burkholderia cepacia complex (Bcc) during initial identification were analyzed by multilocus sequencing (Multilocus Sequence Typing, MLST). 13 genotypes (sequence type, ST) were detected, 9 of them (708, 709, 710, 711, 712, 714, 727, 728, 729) were identified for the first time. Two new alleles for the gene trpB (357, 358), one of the genes atpD (306) and gltB (352) were detected and registered. It was found that strains of 2 genotypes (711, 712) belong to the species B. multivorans, 1 (ST102) - B. contaminans, 1 (ST51) - B. stabilis, 1 (ST729) - B. vietnamiensis. Most strains of the sample, representing 8 genotypes (208, 241, 728, 727, 708, 709, 710, 714), belong to the species B. cenocepacia. Identified genotypes differ in the global spread of the world: 4 genotype (51, 102, 208, 241) have intercontinental distribution, 1 (712) - intra. It is shown that strains causing nosocomial infections, in most cases refer to genotypes 728 and 708. Epidemiologically significant in respect of patients with cystic fibrosis should recognize genotype 709, detected in strains isolated from patients in seven federal districts (FD) of Russia. The Bcc strains of genotypes 241 (B. cenocepacia) and 729 (B. vietnamiensis) were isolated from the patients of the Far Eastern FD. They are not typical for other FD Russia. The possibility of concomitant infection in cystic fibrosis patient with two genotypes 709 - epidemiologically significant and 708 - nosocomial, was indicated. The long-termpersistence of a single genotype strain in the organism of patients with cystic fibrosis was demonstrated as for Bcc species B. cenocepacia (ST 709), so for B. multivorans (ST712). The possibility of transferring the strain Bcc, typical for nosocomial environment to patient with cystic fibrosis at surgery was observed.

[The express diagnostic of microorganisms affecting respiratory tract of patients with mucoviscidosis].

The shared bacteria Burkholderia capacia complex and Achromobacter sp. infect the respiratory tract of patients with mucoviscidosis brining on disorders of respiratory patency. Burkholderia capacia complex is characterized by transmissivity and higher lethality of patients infected by Burkholderia. Hence, the importance of differentiation of these phenotypically similar microorganisms is obvious. The developed express technique of diagnostic includes the separation of DNA from phlegm amplification and sequenation was fragments of genes recA, gltB, gyrB, 16S rDNA. The evaluation of products of amplification of genes recA, gltB makes it possible to differentiate Burkholderia capacia complex and Achromobacter sp. The analysis of successions of recA, gltB, gyrB makes it possible to identify genotype of Burkholderia capacia complex on the basis of data of allele profiles of strains of Burkholderia capacia complex circulating in Russia. The succession of gene 16S rDNA makes it possible to determine the taxonomic position of microorganism dominating in phlegm and not belonging to Burkholderia capacia complex or Achromobacter sp. The real time polymerase chain reaction in presence of intercalating dye Sybr Green I, DMSO and D(+)-trehalose makes it possible to differentiate Burkholderia capacia complex from other microorganisms infecting respiratory tract of patients with mucoviscidosis. This approach provides additional reduction of diagnostic duration and decrease possibility of contamination.

[Effect of halogen aerosol therapy on resistance parameters of the respiratory tract]. / Vliianie galoaérozol'noi terapii na zashchitnye svoistva respiratornogo trakta.

AIM: Assessment of the efficacy of dry high-dispersive aerosol of sodium chloride--the main acting factor of haloaerosol therapy--on defense system of the respiratory tract. MATERIAL AND METHODS: 188 patients with respiratory disease and at risk of pulmonary pathology received course of haloaerosol therapy. 49 matched patients were given placebo. The effect of the treatment was assessed by clinicoendoscopic picture, cytomorphological and bacteriological characteristics of the bronchoalveolar lavage, contamination activity of the microflora, activity of local humoral immunity in pharyngeal brush-biopsies and saliva, rheological indices of the sputum. RESULTS: Dry aerosol of sodium chloride demonstrated antiinflammatory activity in the respiratory tract, mucoregulating action. It enhances drainage of the bronchi, activates alveolar macrophages, improves biocenosis and local humoral immunity. CONCLUSION: Haloaerosol therapy has positive effect on the defense system, improves function of the respiratory tracts.

[Cardiorespiratory system in adult patients with mucoviscidosis]. / Sostoianie kardiorespiratornoi sistemy u vzroslykh bol'nykh mukovistsidozom.

AIM: To study cardiorespiratory system in adult patients with mucoviscedosis. MATERIAL AND METHODS: External respiration function, echocardiographic and dopplercardiographic evidence were analysed for 22 patients with mucoviscedosis. RESULTS: 66.7% examinees had mixed pulmonary ventilation disorders, 46% were found to have low diffuse capacity of the lungs correlating in degree with ventilatory abnormalities. Dilated right heart and high systolic pressure in the pulmonary artery were registered in 14% patients with marked obstruction. Left ventricular systolic and diastolic defects occurred in 23%. CONCLUSION: Adult patients with mucoviscedosis have mixed disorders of pulmonary ventilation, high pressure in pulmonary circulation and developing pulmonary heart in patients with severe obstruction.

[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.

[Effectiveness of the new carbapenem antibiotic, meropenem, in adult patients with mucoviscidosis]. / Effektivnost' primeneniia novogo karbapenemnogo antibiotika-- meropenema u vzroslykh bol'nykh s mukovistsidozom.

Clinical efficacy of meropenem (meronem, Zeneca), a new carbapenem, was studied in the treatment of 4 adult patients with mucoviscidosis. The drug was administered as intravenous infusions 3 times a day in a daily dose of 60 mg/kg body weight for 10 days. A positive clinical effect was observed in 3 patients and in 1 patient stabilization of the clinical state was recorded. A significant decrease in the titre of the Pseudomonas aeruginosa colonies in 2 patients and that of the P. aeruginosa mucosa colonies in 3 patients was bacteriologically confirmed. Good tolerance and no side effects of meropenem in the doses used were stated. The study showed that meropenem may be recommended for the treatment of adult patients with mucoviscidosis.