Since 1990 466 OF patients and more than 1000 members of their families which were clinically diagnosed in the Department of OF of the Research Centre for Medical Genetics have been examined for 20 mutations in the CFTR gene. More than 80% of the patients were originated from the European part of Russia. The relative frequencies of 13 screened OF mutations were as follows: AF508 — 53%, CFTkdele2.3(21kb) – 6.4%, N1303K – 2.6%, G542X – 2.0%, W1282X – 1.9%, – 3849+1 OkbC-T – 1.9%, 2143AT – 1.8%, 2184insA – 1,8%, R334W – 0.7%, S1196X – 0.7%, 394ATT – 0.4%, 1677ATA – 0.5%, G551D – 0.3%. Other screened mutations have not been identified in our sample. The above mentioned 13 mutations account for 75% of all OF alleles of Russian patients. It seems that it is possible to distinguish a nucleos of common “Slavic” mutations (CFTRdele2.3(21kb), 2143AT, 21S4insA) but their origin and history of distribution should be clarified further. Still about 25% of OF alleles are remained to be identified in Russian- population and only for 56% of OF patients the full OF genotype could be recognized. In families where one or both parents have unidentified mutations analysis of inter- andintragenic DNA markers have been exploited to complete genetic testing. As a result the informativity close to 100% could be obtained for all families with the OF child.

The article represents a positive experience of the cooperation between the Russian Cystic Fibrosis Center, the Moscow Department of the Public Health and an Association of Cystic Fibrosis Childrens’ Parents. Such joint work made possible to develop individual treatment schemes and to organize timely outpatient observation of these patients, to provide a treatment continuity of cystic fibrosis patients between the Russian Cystic Fibrosis Center and paediatric outpatient departments as well as Adult Cystic Fibrosis Patients’ Center. It also permitted to arrange a distinct scheme for the full medicine provision and rehabilitation of cystic fibrosis patients and to improve their quality of life, to control precisely and to diminish financial expenses for cystic fibrosis patients’ treatment; to train doctors and nurses of Moscow outpatient departments in cystic fibrosis patients’ management and to improve a quality of outpatient medical care for cystic fibrosis patients.

Cystic fibrosis (OF) is characterized by disorders of chloride secretion and sodium absorption in exocrine epithelium. A crucial location of these ion disorders is the respiratory epithelium. Such ion pathology forms a transepithelial electric potential difference. It is hard to measure tracheobronchial electric potential difference, so a method for measuring nasal potential difference (NPD) was created.

We measured baseline values of NPD in 100 patients (including 45 OF patients) and in 15 healthy volunteers. More significant negative values of the average baseline NPD were registered in the OF patients (42.2±1.4 mV) compared with healthy and COPD persons (-18.3±1.8 and 19.2±0.6 mV accordingly, p<0.0001). NPD values in 6 (13%) OF patients with typical clinical features, normal or boundary sweat test results and CF gene confirmation were compatible with CF bioelectric profile. Meantime 3 COPD patients had increased sweatiest results and a low NPD level.

Under amiloride hydrochloride blocking sodium channels the basal NPD was inhibited greatly (up to 66%) in CF patients, whereas the same value in COPD patients was 36.7%.Therefore, the NPD reflects the principal CF disorder. Its increase under the amiloride influence more than 60% is thought to be used as an additional diagnostic test.

Health care generally changes its tendency from expensive hospitals to cheaper outpatient conditions.
Advantages of a home treatment are an absence of cross- and super-infection risks and of phycologic problems linked to a hospitalization, an economic reasonability. Since February, 1996 the Russian Cystic Fibrosis Center has been practising an antibacterial therapy at home. We performed 189 courses of such the treatment in 44 cystic fibrosis Children during this period. The presence of an intravenous catheter did not disturb a normal life activity of a child and his family, including attendance a school. In 2000 the Moscow Public Health Department and the Russian Cystic Fibrosis Center performed the nurse training in 163 paediatric outpatient departments regarding a care for a peripheral intravenous catheter and infusing through it.

The article constitutes a literal review and an analyze of the author’s private experience in this field. A classification of cough, main causes of its appearance and its complications have been shown. Approaches to the cough diagnosis have been given in detail. It is emphasized that a cough cause is necessary to be estimated. The algorithm for the cough cause recognition developed by the author has been demonstrated. Treatment approaches to a coughing patient have been considered according to the cough aetiology and natural history, and the cough character (productive or non-productive). Finally the author noted that detection of the cough mechanisms and peculiarities allows choosing an efficient therapy for the cough removal or control.

We studed microbiology contamination of bronchial sputum in the 68 sample and other parameters (infectivity, constancy, ecological likeness of bacterias) in 21 adult patients with cystic fibrosis (CF) exaserbation. There were P.aeruginosa, St.aureus and Candida spp. as more often cultures. P.aeruginosa and St.aureus sensitiveness was investigated and we consider that empiric antimicrobial therapy adults patients with exacerbation of CF should consist (include): meropenem (or ceftasidi + netylmicin) + vancomycinum (or rifampicinum) ± fluconasol.

Background – Modulation of the immune response is an attractive alternative approach to therapy in CF. In this regard macrolides with their additional anti-inflammatory properties may be useful in the treatment of CF lung disease. Objective  – to assess action and potential mechanisms of long-term low-dose therapy with 15- and 14-member lactone ring macrolides in children with CF. Methods – Twenty-five CF patients (14 m, 11f; age range 6.5–16 yrs) were treated with azithromycin (SUMAMED^®) in the dose 250 mg 2 times a week or clarithromycin in dose 250 mg every other day and basic therapy (ensymes; mucolytics, including rhDNAse; vitamins). The patients were routinely evaluated every three months. This evaluation included anthropometric measurements (Wt/Ht, %), physical examination, pulmonary function test (FEV₁, FVC), microbiology of sputum (respiratory cultures), inflammatory markers in the sputum samples (neutrophil elastase activity, TNF-α, IL-4, IL-8, IFNγ concentrations) and in peripheral blood (sensitivity of lymphocytes to antiproliferative effect of glucocorticoids). Results – During the six-month period before the start of macrolides most patients had experienced a decline in FVC and FEV1 (-3.3±2% and -2±1.5% predicted, respectively). Following the treatment the lung disease progression became slower (FVC: 7.0±2.1% and FEV1: 7.1±2.1%, both p=0.02). The effect was more pronounced in the patients with FVC<70 %. Before macrolides treatment this subjects showed a loss of the mean semiannual changes in FVC (-6.0±3.0%) and FEV1 (-3.3±2.4%). After six month treatment with macrolides we noticed a significant improvement in lung function (FVC: 8.6±3.6 %, FEV₁: 9.4±3.0%, both p=0.03). The patients with poor lung function showed an essential elevation of neutrophil elastase activity (from 60.0±15.1 to 130.1 ±30.4 U/mg protein; p=0.05) and decrease of TNF-β (from 68.0±34.1 to 9.3±2.3 lU/mg protein; p=0.02) in their sputum. Authors postulate that elastase activity elevation is associated with destruction of neutrophils following the antiinflammatory treatment. Discussion – Our preliminary findings suggest some potential mechanisms, by which long-term low-dose 15- and 14-member lactone ring macrolides therapy may be beneficial in CF.

The purpose of our study was to examine the antiinflammatory effect of nimesulide the novel selective cyclooxygenase-2 inhibitor. Fifteen CF patients (the mean age 11.9 years) were treated with basic therapy and nimesulide in the daily dose of 3 mg per kg of the body weight. Inflammatory markers in the sputum samples (neutrophil elastase activity, TNF-α and IL-8 concentrations) and in peripheral blood (sensitivity of lymphocytes to antiproliferative effect of glucocorticoids and plasma TNF-α level) have been determined. During the six-month period before the start of Nimesulide, most patients had experienced a decline in FEV₁ and FVC. Following the nimesulide treatment the lung disease progression became slower. The patients with poor lung function showed an essential elevation of neutrophil elastase activity and decrease of TNF-α in their sputa. Authors postulate that elastase activity elevation is associated with the destruction of neutrophils following the antiinflammatory treatment. Decrease in plasma concentrations of TNF-α as well as in the number of activated lymphocytes in peripheral blood is an evidence of the systemic antiinflammatory effect of nimesulide.

From 455 Cystic Fibrosis patients 10.2% has liver cirrhosis. In Russia we were the first to introduce surgical means of treatment for portal hypertension in CF patients with liver cirrhosis. Sclerotherapy and portal venous shunting are used if variceal haemorrhage occurs. It was shown that all of them were palliative manipulations: portocaval shunts provided good control of portal hypertension but intensified liver failure, sclerotherapy did not prevent a recurrence of bleeding. In the future liver transplantation will be introduced for Cystic Fibrosis patients in Russia.

25 patients with CF and 20 with others of COPD were examinated. Ciliary beat was measured by a lifetime TV microscopy of bioptates of respiratory mucous. Material was obtained with the help of brush biopsy during fiberoptic bronchoscopy. The image of ciliary beat from a light microscope was recorded on the hard disk of the personal computer. The specially created program estimated ciliary beat frequency (CBF) and amplitude of ciliary beating. CBF into bronchi of the CF patients have made at impact phase – 6.3+0.33 Hz, raising phase – 5.7+0.36 Hz; in the patients with COPD: 6.5+0.32 Hz and 6.2+0.33 Hz accordingly. The precise tendency to a drop of CBF and amplitude of ciliary beating in the patients with CF on a comparison with the patients with COPD and literary datas was marked. Also, the drop of indexes of beating in the patients with Ps.aeruginosae mucoid were marked.

The aim of our work was to search specificity and sensitivity of pancreatic elastase-1 (E-1) immune enzyme detection (ScheBo^®BloTech, Germany) in faecal material both to define pancreatic failure in cystic fibrosis (CF) patients and to diagnose CF. The trial group included 128 children. The main subgroup involved 112 CF patients including 4 ones with CF pulmonary form aged from 3 months to 19 years. The control group involved 16. conventionally healthy children of the same age with no obvious digestive injury.

The E-1 concentration in all the control group children was within the normal range (more than 500 mcg/g of the faecal material), thus, the specificity of the method was 100%. Meanwhile, the sensitivity of the pancreatic failure detection in the CF patients was 86.6%. Moreover, we revealed the negative correlation (r =0.4; p<0.001) between E-1 concentration and a dose of a pancreatic enzyme drug (a lipase unit per 1 kg of the body weight in a day) taken by patients.

Therefore, the faecal detection of E-1 is a simple, exact and non-invasive method for pancreatic failure diagnosing in CF children; therapy with pancreatic enzyme drugs does not influence the result. The E-1 level detection can help to select a pancreatic enzyme replacing dose in CF patients. If the E-1 level is normal, the reasonability of pancreatic enzyme drug administration should be revised. When monitoring E-1 level in CF patients with preserved pancreatic function it is possible to administrate pancreatic enzyme drugs timely.

The aim of the multicentre study was to set up the national register and evaluate survival of patients with cystic fibrosis in Russia. Data were provided from the six special cystic fibrosis clinics and were used for national register. Six hundred thirty three patients (292 females and 341 males) were analysed.

One hundred eighty two patients were over 15 years (17%). In the beginning of the analysis, 107 patients (17%) were registered dead. Survival analysis has demonstrated that the mediana of expectant life is 25 years. It has demonstrated that significant difference exists in expectation of life between sexes (p=0.045). The mediana of expectant life in men is 29 years, whereas this parameter in women is 22 years. Our data have confirmed that cystic fibrosis is actual problem of pulmonology and isn’t only paediatrics problem any more.

The frequency of appearance and structure of internal diseases were estimated as well as their genetic premises in 83 parents of patients with CF. These results were compared in 68 parents of patients suffering from lung diseases without genetic determination. This study showed that the character features of parents of CF patients who were obligate heterozygotes of CF gene is high frequency of respiratory (25%) and digestive (42%) diseases. The predisposition to lung diseases was higher in mothers of CF patients with ∆F508 mutation of CFTR gene. Haplotype HLA A1B40 was regarded as risk factor to forming lung diseases.

The results of six-year health-care system efforts in antiasthmatic program dedicated to the implementation of the principal guidelines of GINA were evaluated in Smolensk city. The educational programs for physicians and patients, and financial support of preferential release of antiasthmatic drugs have led to the radical changes in basic treatment of bronchial asthma. During the six-year period, the 23-fold increase in the proportion of inhalation glucocorticoids use has been accompanied by 1.7- and 1.5-fold decrease of the use of system steroids and cromoglycates, respectively. At the same period of time, in Smolensk the number of ambulance calls for asthmatic attack, the emergency hospitalization, the rate of disablement due to asthma, and primary disablement have been decreased 2.4, 2.3, 1.7, and 3.3 times, respectively.

The aim of the study was to assess results of long-term treatment of chronic obstructive bronchitis (COB) patients performed by therapeutists trained according to the Federal programme on COPD.

Treatment results of 151 COB patients (100 males and 51 females) were analyzed. The average age of the patients was 51.8±0.8 years. The long-term treatment was carried out in accordance to the algorithm of the basic therapy of COPD.

The significant positive changes in the patients’ clinical status were noted at the end of the 3rd week of the therapy: a cough frequency reduced in 96.7% of the patients and a dyspnoe severity decreased in 95.4% of them. The peak flow rate parameters improved reliably. Seventy three moderate to severe COB patients had received the basic medication during 12 months showed decreasing cough and dyspnoe seventy and improving peak flow rate parameters though these changes were less intensive than in the first 3 weeks of the treatment.

So, the investigation demonstrated a possibility to inhibit the bronchial obstruction and COB clinical signs progression under the background of the long-term basic therapy.