«íåêîììåð÷åñêîå ïàðòíåðñòâî «îðãàíèçàöèÿ ïîìîùè ...»
Also the Association takes an active part in public and cultural life of the city. For example, with the active participation of the Saratov AAPCF in the city a beauty contest among people with 72 Problems and achievements in treatment of patients with Cystic Problems and achievements in treatment of patients with Cystic Fibrosis in Russian Federation and abroad Fibrosis in Russian Federation and abroad Unlimited possibilities «Eighth wonder of the world» was carried out. It showed that nothing is impossible – we need just to want!
Experience and achievements of our Association in the region serves as an example for other organizations that help people with disabilities.
Thanks to the assistance of charitable funds and the pharmaceutical companies, patients CliniCal signiFiCanCe oF the mass sCreening who are in dire need have the expensive medications;
patients have inhalers, thermodisinfectors and other means of individual rehabilitation.
on CF in newborns Now, in Russia many charities help patients with cystic fibrosis address. Only the charitable Fund «OSTROVA» came to the problems of cystic fibrosis globally, and this helped to change Kapranov N.I., Kusova Z.A., Sherman V.D.
radically the attitude of the society and the authorities to such patients.
For the first time in Russian history, cystic fibrosis in 2011 was held three competitive Scientific research center of medical genetics, Moscow projects of the charity Fund «OSTROVA» within the framework of «I breathe».
«Kinesitherapy» - creation and the work of the offices of kinesitherapy in different regions Cystic fibrosis (CF) remains an important medical and social problem of developed of Russia;
the «Initiative» - a contest of patient’s organizations’ projects;
«Shopin prize» - a countries.
support for active young people diagnosed with cystic fibrosis. Progress in its studying gave a stimulus to development of fundamental and applied In addition, already now one can see the positive results of the implementation of the medical, pharmaceutical, biotechnological and other sciences.
programme. The opening of the six rooms of kinesitherapy (Saratov, Samara, Voronezh, Tomsk, Over the past two decades in the study of the CF, enormous progress was achieved.
cystic fibrosis. Patients, their parents understood that with such a diagnosis, they can live a In the Russian Federation for the past 10 years a network of regional CF centres (their long, high-quality and fully life, and the most important thing is that personal activity gives number now - 52) was created, they provide an active dispensary observation of patients CF, good results in solving different problems. introducing adequate, modern technologies and methods of treatment and rehabilitation The contest «Øîïåíîâñêàÿ prize» showed that adult patients with socially significant life into practice.
position, self-actualize, do not retreat into themself and are confident in tomorrow’s day. Their This, of course, improves quality and increases life expectancy of patients. Moreover, the ability to live is an example and an incentive for other patients and their families, as well as for increase in the number of adults living with CF, stimulates the organization of centers for all people with disabilities. diagnosis and treatment, along with a number of positive aspects, aims to specialists, the new objectives, representing an undoubted scientific interest, have the important practical value.
This is, first the clinico-functional diagnostics of the disease, its unusual manifestations and complications, such as infertility (male and female), ENT-pathology, diabetes, osteoporosis, liver cirrhosis, pneumothorax, hemoptysis and bleeding (lung, stomach), cor pulmonale, etc.
In connection with the above, the clinical significance of mass screening on CF is evident, because of early diagnosis and well-timed adequate modern therapy, along with other factors, have positive impact on the quality and life expectancy of the patients of this group. Neonatal screening implies the possibility to early genetic counseling (prior to conception of the next child), which can affect the reproductive conduct of spouses and their relatives. Therefore, after the introduction of screening Programs in France (region of Brittany) there was a reduction in the frequency CF in newborns on 15-30%. In addition, the neonatal screening allows reducing the stress for parents, associated with deferred diagnosis.
A great role in solving of important medical and social problems is played by the newly established public organization «all-Russian Association of assistance to patients with CF,»
the charitable Fund «OSTROVA», «In the name of life», public organization of parents “Care of patients with CF”.
74 Problems and achievements in treatment of patients with Cystic Problems and achievements in treatment of patients with Cystic Fibrosis in Russian Federation and abroad Fibrosis in Russian Federation and abroad the oBjectives oF Future research on the ProBleM oF cF shoulD Be:
• Evaluation of the effectiveness of mass screening of newborns for CF;
• Determination of the clinical significance of the constant transformation of bacterial pathogens;
• The development and widespread introduction of new, sensitive methods of functional dynamiCs oF amount and Change oF age struCture diagnostics of lung disorders (ERF, CT, etc.);
• Monitoring of the effectiveness of the current treatment (intravenous antibiotic therapy, oF Patients with CF in mosCow and the mosCow inhalation antibiotics, steroids, etc.);
region For the Periods 1992-2001 and 2002- • The development and implementation of the work of the regional CF centres;
register of patients with the annual report;
• Diagnostics and treatment of complications (pneumothorax, bleeding, diabetes, Krasovsky S.A., Chernyak A.V., Amelina E.L.
• The interaction of the genotype with clinical manifestations of the disease;
the Scientific research institute of pulmonology, Moscow development of an objective assessment of the effectiveness of the targeting gene therapy of CF.
The city of Moscow and Moscow region are major subjects of the Russian Federation with All of the above will contribute to the further improvement of quality and life expectancy a total population of about 18-19 million people.
of the patients with CF. Since 1992, the patients with CF, who live in Moscow and the Moscow region, are receiving outpatient treatment in the Russian center of Cystic Fibrosis on the basis of the N.F.Filatov Children’s city clinical hospital, in-patient treatment in the Russian Children’s Clinical Hospital and Research Center of Children Health of Russian Academy of medical Sciences. When reaching the age of 18 patients move under the supervision of the research Institute of Pulmonology of FMBA of Russia on the basis of the City clinical hospital ¹ 57, Moscow.
the aiM oF the work Is to estimate the dynamics of the total number and age structure of the patients with CF for the 20-year period from 1992 to the year 2011.
Materials anD MethoDs The outpatient cards of patients registered at the Moscow CF centers at 01.01.2002, and 01.01.2012 were analysed. Diagnosed with cystic fibrosis was established considering the clinical manifestation and/or a positive neonatal screening, positive sweat samples and/or discovery of two mutations in a gene CFTR or discovery of two mutations.
Statistical processing of the results was carried out using the program Statistica for Windows 7.0.
results anD Discussion A characteristic of the involved group is represented in the table. 1.
The age structure of the patients is shown in Fig. 1 and table. 2. The change of the structure of the patients, by main age periods is noticed, for the last decade the proportion of patients infants and young children and adult patients has reliably increased, while in the previous decade the age groups of school and adolescence was dominating.
76 Problems and achievements in treatment of patients with Cystic Problems and achievements in treatment of patients with Cystic Fibrosis in Russian Federation and abroad Fibrosis in Russian Federation and abroad neonatal screening program, only in Moscow 75 patients with CF were found for 5.5 years. The table 1. Characteristic of the involved groups start of neonatal screening, allowed to significantly increase the number of patients infants Period 1992 – 2001 2002 – 2001 P and young children who occupied a significant share in the total structure of the patients in Total, n, (M/F) 201 (108/93) 425 (223/202) the last decade - 77 people (18,1% of the total number of patients).
Age, yrs., median ± SD (min-max) 12,3±7,1 (0,32-36,7) 13,4±9,7 (0,16-44,3) 0. In addition to neonatal screening, over the last decade diagnostics of CF has been improved Died, n (% of total), M/F 26 (13,0), 8/18 50 (12,0), 26/24 0. in all age groups, including in patients older than 18 years old, so for the period 2002-2011, the Age of died, yrs., median ±SD 17,7±9,5 (0,32-36,7) 17,5±8,7 (0,5-40,2) 0.09 diagnosis was confirmed in 22 adult patients, while for the period 1992-2001 – only in 4. Late (min-max) diagnosis of the CF is due to both a «weak» knowledge about this disease by the majority of Patients aged 18 yrs.
1-3 6 (3,0) 55 (12,9) 0, A favorable impact on lung function provides treatment of low doses of macrolides, which 3-7 42 (20,8) 73 (17,2) 0, in the last decade routinely prescribed with anti-inflammatory order to patients with chronic 7-12 55 (27,4) 60 (14,1) 0, Pseudomonas infection.
12-18 57 (28,4) 80 (18,8) 0, Significant changes have occurred at the turn of the centuries in providing assistance to the 18-30 35 (17,4) 114 (26,8) 0, heavy patients. It is an outpatient oxygen therapy, non-invasive lung ventilation, embolisation 30 and older 3 (1,5) 21 (5,0) 0,001 bronchial arteries.
Over the last decade have been optimized and changed some of the approaches to the use of systemic antibiotics, their doses and combinations, new antibacterial drugs were widely introduced in practice, the carried over bronchodilators. The use of hepatic and anti-inflammatory therapy became routine. In recent years, the especial attention is paid to the prevention and treatment of frequent extra-pulmonary complications of CF: osteoporosis, diabetes, cirrhosis of liver, electrolyte disorders, which can significantly aggravate the general course of the disease and even lead to death. Improvement of methods of kinesitherapy is being continued.
A particularly important aspect of the management of patients is the work of the centres of CF, which are concentrated in the disease and all the latest knowledge in the field of diagnostics and treatment of this pathology.
From the institutional component of treatment in children and adults centers, it is necessary to note the commitment of outpatient approach in carrying out of courses of intravenous antimicrobial therapy that allows maintaining a high level of quality of life and prevents infection of the respiratory tract by gram-negative flora for a long period;
this positively affects the respiratory status of patients.
à b conclusion Fig 1. age structures of patients for 1992-2001 (a) and 2002-2011 (b) Over the last decade, the total number of patients in the Moscow region has more than doubled, driven by improved survival and diagnostics of cystic fibrosis in all age groups. In These results show advances in the diagnosis and treatment of CF in the last 20 years the improvement of the diagnosis, the beginning of neonatal screening and more careful in Moscow and the Moscow region. The significant growth of the total number of patients identification of the disease in patients over the age of 18 years played a great role. The occurred not only because of the improved survival as such, as is expressed primarily in the emergence of new drugs for the treatment of cystic fibrosis, optimization of some of the increase in the percentage of adult patients, but also because of improvement of diagnostics medical and organizational approaches and the accumulation of experience have influenced of CF. Started in Moscow in July 2006, and in the Moscow region since January 2007, neonatal on improvement of survival.
screening for CF had played a significant role in it. Therefore, for the time of operation of the 78 Problems and achievements in treatment of patients with Cystic Problems and achievements in treatment of patients with Cystic Fibrosis in Russian Federation and abroad Fibrosis in Russian Federation and abroad conclusion There is a direct dependence of the basal metabolism on the severity of cystic fibrosis (cf with the increase of severity), and clear dependence on an infectious process (when the accession of Pseudomonas infections increase the exchange). All patients with cystic fibrosis require nutritional support because of a significant increase of the basal metabolism. The PeriCuliarities oF basal metabolism and possibility of correction of the feeding insufficiency at the expense of mixtures is high enough.
Revealing of infringements of the metabolism of carbohydrates dictates the obligation of nutritiVe suPPort oF Patients with CF control of blood glucose level on the background of additional injection of mixtures and their individual selection.
Strict observation of this group of patients with careful measurement of the energy losses, Orlov A.V., Pashkevich A.A.
including the measurement of basal metabolism, is very important for the optimization of nutritional support with the account of the etiology of infectious process, the age and degree Saint Olga’s hospital, S -Petersburg of severity of disease.
aiM oF the stuDy A research of the relationship of the basal metabolism in patients with cystic fibrosis with the course of the disease and the infection process.
Materials anD MethoDs 23 patients with the mixed form of cystic fibrosis were involved into the study;
the diagnosis is confirmed by genetic test. Of them, 15 boys and eight girls three children of 3 to 6 years of age, nine children of 7 to 11 years of age, 11 children of 12 years of age and 2 persons of years of age. On the basis of the analysis of the external respiration function, periculiarities of microflora, weight-and-growth rates and frequency of exacerbations, the moderate severity of the disease was observed in 11 children, and severe form in 12. All children were examined in the period of remission. Patients underwent a study of the function of external respiration, analysis of sputum, determination of weight-to-growth index and body mass index.
For the first time in Russia a study of basal metabolism in children with cystic fibrosis was carried out using the device «Fit mate PRO». Measure of basal metabolism is calculated as a percentage to the values and depends on the volume of inhaled oxygen in ml/min, gender, age, height and body weight. The studies were carried out within 15 minutes, with a comfortable ambient temperature (18-20 degrees C), in the lying position, in a state of emotional calm, through 12-16 hours after the last meal, excluding daily loads.
The additional food mixes (Pediashure and Nutridrink) were prescribed at the rate of to 900 ccal\day for 1 month according to the level of increase of the basal metabolism and degree of chronic protein-energetic insufficiency. One patient took a night tube feeding with a mixture Peptamen junior.
results anD Discussion The basal in all patients with cystic fibrosis is above the age norm. Considering the statistical evaluation according to the criterion of the Mann-Whitney, the metabolism was significantly higher in the group of patients with chronic Pseudomonas infection (p=0,0167). There is a tendency to the increase of the basal metabolism with the exacerbation of disease severity (p=0,0935) and with increasing of patient’s age (p=0,0628).
All patients gained weight by 0.8-1 kg in a month. Change of the basal metabolism for this period is not observed. In eight patients on the background of admission of mixtures, there was a disturbance of tolerance to carbohydrates.
80 Problems and achievements in treatment of patients with Cystic Problems and achievements in treatment of patients with Cystic Fibrosis in Russian Federation and abroad Fibrosis in Russian Federation and abroad in the younger and older group the rates are similar and are 60-80% of MGI, that is explained by the shorter duration of the therapy in younger groups, and in older groups also by stable morphological changes in the affected organs. In addition, the duration of disease involves slowly growing negativism to medical procedures. In addition, of course, workload affects to this, because as a rule, our cystic fibrosis patients often have many talents and willingly Problem oF CystiC Fibrosis in Kaliningrad region promote creative abilities, are actively involved in school life. Either there is a greater variability of nutrition status depending on the frequency and severity of exacerbations.
Most of the children in our region received a full treatment in the last five years, which is Petrov V.N. connected with the inclusion of Pulmozyme into the list of drugs of the program « The seven nosologies». At the background of treatment in patients, we noticed a significant increase of Regional children’s hospital, Kaliningrad the spirometry rates, first ERF. All rates of external respiration in most cases are connecteded directly proportional to the nutritive status. The values of external respiration decline with The population of the Kaliningrad region in 2011 amounted to 940 thousand people. fall in the supply, and, first, the FVC reduces. The greatest deviations of ERF we observe in the Of them, there are children 172 000 aged from 0 to 17 years. The population was formed in older age group, which is certainly due to the late introduction of the Pulmozyme therapy, 1946-1947, when there was a full reset because of the eviction of the German population and the presence of the expressed morphological changes in the lungs, chronic colonization of resettlement in the region of the inhabitants of various regions of the European part of the Escherichia coli, low nutritive status and, consequently muscle weakness. Nutritional support USSR, mostly of Slavic nationalities. In subsequent years, the migration processes give rise to for the younger children is the mixture Nutrien Pulmo, the senior - Nutridrink. The problem the Diaspora of the southern peoples. Currently in the region, there are 13 children with cystic is the relatively high cost of those mixtures. Our patients get them for the account of the fibrosis (CF) of Slavic nationalities and one of Armenian. More than 10 years ago the creation sponsor’s assistance or additional financial burden is on the family of the patient.
of a regional center of cystic fibrosis on the basis of the pediatric department of the regional In recent years, we note a better support for our patients with antibiotics of the reserve children’s hospital for observation and assistance to this category of patients of children living (Fortum), with anti-P.aer. activity, in particular with imepenem, but the problem remains in in the Kaliningrad region. In the vast majority of cases, the diagnosis was made on the basis the provision of inhaled antibiotic - tobramycine and colistin. Patients with CF receive inhaled of the clinical manifestaion with the subsequent verification on the basis of skin test, reliable antibiotics due to the sponsor’s assistance as a result of telethons, and the practical assistance reduction of the content of trypsin and elastase of feces, with the subsequent genetic testing. which is often provided by the Centre of cystic fibrosis of the land of Schleswig-Holstein Prenatal diagnosis (concentration of immunoreactivity of trypsin in a dry spot of blood of (Germany).
the newborn) gives both false positive and false negative results. This stresses the need for Thus, in 2011, all patients were invited to the course of kinesitherapy, where among other continuous surveillance to determine the diagnosis. So, for the last 3 years the by methods things, they received a month’s supply of tobramycin and colistin.
of prenatal screening only one patient was revealed, the diagnosis is not subsequently We have submitted applications to the regional Ministry of health for the free provision of confirmed in the same period, were 2 patients were clinically identified, the diagnosis was later patients with tobramycin and colistin, however, in view of the frequent personnel changes in confirmed by the positive sweat test, the decrease of the level of trypsin and elastase feces the Ministry, the question is still not solved.
and genetically. The problem is the absence of the sweat analyzer in the region, although in the next year we expect the acquisition in the framework of the modernization of health care.
The number of patients with cystic fibrosis is 19 people, of which there are 14 children aged from 0 to 18 years. The incidence of cystic fibrosis is 1: 50 000. The incidence of cystic fibrosis in the region is 0.11 per 1000 of the child population, 10 boys and 4 girls. Severe course of the disease is observed in 8, easy - in 3, moderate - in 3 patients. Age structure: 2 children aged 0- year, 1 child aged 3 to 6 years, 4 children aged 7-11 years and 7 children in the age of 11- years. Intestinal form of CF is observed in three patients in the light form, in 11 patients there is a mixed, mainly the pulmonary form.
Four patients have chronic colonization of Ps. Aeruginosa, Burkh.cepacia single planting - in two patients and chronic infection Staph.aureus – in three patients with severe course.
In children with severe course and with moderate CF similar genotypes were identified, but occurred with varying frequency. In our region in patients with severe fairly there are often met unspecified mutations, and in moderate - DelF508.
We estimate nutritive status of the patients with the method of determining the mass growth index and additionally by centille tables. In the assessment of nutritive status, the better rates of the mass growth index occur in children from 3 to 11 years - from 86 to 100%;
82 Problems and achievements in treatment of patients with Cystic Problems and achievements in treatment of patients with Cystic Fibrosis in Russian Federation and abroad Fibrosis in Russian Federation and abroad manifestations of the gastro-intestinal tract with the first months of life. Both are constantly taking Pulmozyme in the dose of 2.5 ml and CREON. The child 10 years of age has more severe course of the disease. On CT of the chest there is a clinical presentation of deformative bronchitis, bronchiectasis, there were frequent exacerbation of bronchopulmonary process, frequent maxillary sinusitis, the girl is a carrier of pathogenic Staphylococcus. Pulmonologist analysis oF CystiC Fibrosis morbidity in rePubliC and genetics regularly observe the child;
2 times a year she gets inpatient treatment and examination. During the last 2 years, the condition has stabilized. In 2011, she was examined at oF Karelia in 1996 – 2011 the RCCH in Moscow. Girl 2.5 years of age: the last hospitalization in March 2011 to ÎÄÌ ÄÐÁ, from this moment receives Pulmozyme, lives in the region, there is no regular supervision, and Kutuzova N.G., Kuleshova E.V., Novozhilova T.C.
hospitalization to ÀÏÖ ÄÐÁ in April 2012 is planned. In terms of the referral of the child to the Central base for more in-depth examination and corrections of therapy.
Republic children’s hospital. Medical-genetic consultation of the republic of Karelia Thus, in Karelia there is a low percentage of incidences of cystic fibrosis. Previously high incidence rates are explained by the impossibility of genetic examination. Diagnosis was Cystic fibrosis is an inherited disease, which arises because of a mutation of genes and confirmed on the basis of clinical manifestations (recurrent obstructive bronchitis, dysfunction characterized by pronounced genetic heterogeneity, clinical polymorphism, severe course of the intestine, manifestations of malnutrition) and the high rates of sweat tests.
and prognosis. The frequency of occurrence of cystic fibrosis in Russia is 1:9000 of newborns. In connection with the development of new approaches of data on patients and more effective medical support, their life expectancy increases. Now in the medical-genetic consultation of the Republic of Karelia there are 27 people registered, including 3 children and 24 adults. Of the 27 people, 17 patients passed the DNA-test.
For the past 15 years, eight people are under the doctor’s care, five of them are male patients, and three are female. Of the eight patients, one child was identified for neonatal screening. Cystic fibrosis was diagnosed within the neonatal age of two children, from 2 to 5 months of life - 2 children, at the age of 1 year – 1child, in 4 years of age – 1 child, from to 14 years of age - 2 children. The diagnosis was defined in seven children on the basis of medical-genetic consultation CRH of Petrozavodsk, 1 child was diagnosed in research Institute of Children gastroenterology of N. Novgorod. Five patients were examined on the central bases: three patients in the research Institute of Pulmonology of Saint Petersburg, 1 patient at the RCCH of Moscow and 1 patient in research Institute of Children gastroenterology of N.
Of eight persons, delivered to the account, the following forms of the disease were identified: in six patients - pulmonary form, in two - mixed. DNA-diagnostics was carried out for all patients. For the past period two of the children died, one of them in the neonatal period after surgical treatment of the meconial ileus, the second in 6 months of age because of acute respiratory failure. In both children the diagnosis was confirmed after the pathological anatomy examination, DNA diagnosis also was made. Regularly observed in the genetics of 11 people, the rest of the patients at the reception are not, despite repeated invitations. The reasons for failure to appear for examinations to genetics are:
• Overdiagnosis in the early age, without further genetic confirmation of diagnosis;
• The remoteness of the place of residence of patients;
• Socially troubled families (7 patients);
• Change of the place of residence and the names of patients without notice genetics.
Nine people receive a specific therapy with Pulmozyme and two of them are children.
Now in ÀÏÖ CRH two girls with cystic fibrosis (2.5 years old and 10 years old), with a mixed form of the disease are observed. The diagnosis is confirmed genetically in 10-year old girl at the age of 4 years, with clinical manifestations from 2 months of age on the part of the upper respiratory tract. The second child is diagnosed at the age of 1 year, with clinical 84 Problems and achievements in treatment of patients with Cystic Problems and achievements in treatment of patients with Cystic Fibrosis in Russian Federation and abroad Fibrosis in Russian Federation and abroad results OGTT was held in 64 patients;
normal carbohydrate metabolism only in 51,5% of the surveyed patients MV was identified, IGT was revealed at 29.7% of patients, and CFDD at 18. per cent (criteria of the WHO, 1999). (Fig.1).
morbidity oF Carbohydrate metabolism Figure 1 oral glucose tolerance test (ogtt, n=64) malFunCtions and their inFluenCe on the Course oF disease in adult Patients with CF Samoilenko V.A., Krasovsky S.A., Babadjanova G.Y., Chikina S.Y.
Scientific research institute of pulmonology, Moscow introDuction Adult patients with CF were allocated into 3 groups by the results of OGTT as follows:
Abroad the development of diabetes in patients with CF is actively studied over the past • without disorders of carbohydrate metabolism (217 pers.);
30 years. According to various authors, the morbidity of diabetes in CF is ranging from 2.5% to • with impaired tolerance to glucose (19 people);
32%, increasing in proportion to the age of the patients. Therefore, according to Ali B.R. (2009) • with CFDD (36 people);
diabetes develops in 15% of patients with CF, and in patients older than 30 years, this figure reaches 50%.
We revealed that patients with ÌÇÑÄ have a low BMI (17,3 against 18, 4kg/m2, p0.05), According to Russian scientists, impaired glucose tolerance (IGT) is found at 50-75% of lower growth (163,4 against 169 cm, p0.05) and body weight (46,6 against 52.9 kg, p0.05) patients, and clinically diabetes manifests in 5-15%. There were no studies of differences while comparing these groups and these differences are reliable (table. 2).
between patients with cystic fibrosis-dependant diabetes (CFDD) and adults with CF with normal carbohydrate metabolism in Russia.
table 2. Characteristics of adult patients with CF without dCm, with igt and CFdd.
the aiM oF the research CF without DCM CF with IGT (n=19) CF with CFDD (n=36) (n=217) To study prevalence of disorders of carbohydrate metabolism (DCM) - CFDD and IGT, and the clinical features of adult patients with CF and DCM in comparison with other adults Age 25,6 ± 5,6 25,1 ± 6,8 23,9 ± 3, patients without the disturbances of carbohydrate metabolism. Gender m/f 103/114 9/10 18/ Material anD MethoDs Growth, cm 169 ± 9,3 167,7 ± 9,9 163,4 ± 10,1* The study included 272 patients, with an average age of 25.3 g.;
in this group, there were Weight, kg 52,9 ± 10,8 52,2 ± 9,0 46,6 ± 10,4* 130 men and 142 women, anthropometric signs are represented in table 1.
BMI, kg/m2 18,4 ± 2,8 18,6 ± 3,1 17,3 ± 2,7 * table 1 general characteristics of patients with CF * p0,05 (CF without DCM and CFDD) The bodypletizmography in patients with CFDD had shown significantly more low values Age 25,3 ± 5, of lung function than patients without HMD (average% of the proper – FEV1 68.0 against 81,9, Gender, m/f 130/ FEV1 48,2 against 66,4 and the Tiffno samples 60,1 against 67,6, p0.05), Fig. 2.
Growth, cm 168 ± 9,6 The bacteriological examination of sputum in the group of patients with CFDD had revealed a fairly low colonization of St. Aureus (5,5% against 25.8 percent, p0.05 (x2) and a Height, kg 52,1 ± 10, larger percentage of the B. Cepacia (32,7% against 15.2 percent, p0.05 (x2) in comparison BMI, kg/m2 18,3 ± 2, with the group without CFDD (Fig. 3).
We have carried out the bodyplethismography, bacteriological examination of sputum to the patients;
oral glucose tolerance test (OGTT) was performed by the method of random sampling to determine the glucose level fasting and 2 hours after taking of 75 g of glucose.
86 Problems and achievements in treatment of patients with Cystic Problems and achievements in treatment of patients with Cystic Fibrosis in Russian Federation and abroad Fibrosis in Russian Federation and abroad Figure 2. the functional parameters of the respiratory system main asPeCts oF organization oF ambulatory Care For Patients with CF in samara region Vasil’eva E.A., Katkova L.I., Morozova L.A., Ivanova N.N.
Children’s city clinical hospital ¹ 1 of Samara The Ministry of health and social development of the Samara region Figure 3. Colonization of pathogens in the sputum in CF without CFdd and with CFdd.
Samara regional Association of aid to patients with cystic fibrosis In the last 17 years in Samara and the Samara region, a specialized Centre in close cooperation with the Association of aid to patients with cystic fibrosis and the Ministry of health and social development of the Samara region is concerned with the question of the organization of assistance for patients with cystic fibrosis (CF). The center was organized on a functional basis of the infectious boxed department of the N.N. Ivanova Children’s city clinical hospital ¹ 1 in and initially functioned for the city. In 1999, the Centre has acquired the regional status, where assistance had been started for provision to all patients with CF: children and adults. For 17 years of work of the centre, the number of patients has increased from 30 to 93 people. This happened due to the improvement of the quality of diagnostics, the early prescription of basic therapy and improvement of drug supply at all stages of aid. In the Samara center there is the entire complex of measures according to the standard of care of CF, the latest methods of examination and treatment are successfully applied, allowing patients to maintain a full life. To provide skilled conclusion care the center cooperates actively with Samara state medical University, and with the leading Thus, the prevalence of CFDD in adult patients with CF is high enough, and the CFDD is specialized centers of the Russian Federation for the treatment of cystic fibrosis (Moscow, St.
identified in each of the second adult patient with CF. Petersburg, etc.). Now in the Samara centre 93 people with different forms of the disease at the The CF in adults, complicated by the CFDD, has its own peculiarities: age from a few months up to 35 years are under the supervision.
• Latent period;
As is known, in cystic fibrosis the process of therapy can be successful only in case of its • Retardation of physical development of the patients;
continuity. The most important question that can be solved only by joint efforts (Center + MH • Lower pulmonary function follows;
and ÑÐ ÑÎ + parents’ Association) is providing of patients with CF with the medicines (drugs) at • Microbiological profile changes into the more aggressive. all stages of treatment. The necessary conditions for the solution of this problem are as follows:
Work with the legislative and executive power.
• Determination of the required volume of drugs for a month, quarter, year.
• Calculation of the required cash.
• Drawing of nominal lists of the distribution of drugs with the indication of the health institutions, in which our patients are under supervision.
• Monthly monitoring of drug provision of patients.
Sources of ensuring patients MV drugs for outpatient treatment are:
The Federal budget:
• A program of care for patients with the seven high cost-based diseases (7 of CB). On this program, our patients receive a drug Pulmozyme.
• Program of essential medicines (PEM) - CREON, Ursosan, Fluimucil, etc.
88 Problems and achievements in treatment of patients with Cystic Problems and achievements in treatment of patients with Cystic Fibrosis in Russian Federation and abroad Fibrosis in Russian Federation and abroad The budget of the Samara region:
• The program of regional drug-support - RDS.
Under the program of RDS, our patients receive the essential expensive drugs missing in the programme PEM. These are mainly antibiotics, including drugs for parenteral taking. Due to the order of the MoH and ÑÐ ÑÎ, the hospital patients with severe cystic fibrosis have the morbidity oF CF in Children in arKhangelsK region.
opportunity to receive courses of anti-relapse antimicrobial therapy on an outpatient basis (in day hospitals and at home).
Thus, all the patients with CF, which are registered in the centre, receive the necessary Smirnova G.P., Smorodina Y.V., Eivazova E.A., Bykova A.V., Ozderkhanova N.V.
assistance as at the stage of stationary and ambulatory treatment. Because of our activities, we would like to note the significant decrease of mortality of patients with cystic fibrosis and North state medical university, Arkhangelsk.
to improve the quality of their life;
the active integration of our patients in the society - they «Arkhangelsk chidren’s clinic hospital»
attend the school, study at Universities, and they are engaged in creative work.
The prevalence of cystic fibrosis the Arkhangelsk region is 1: 10 214 of the child population.
16 children and 5 teenagers are under supervision about this disease, a total of 22 patients in the age from 3 months to 17 years, the average age is 8.2 years. The definition of genetic mutations is carried out in the medical-genetic laboratory ÃÁÓÇ «ACCH» at the 9 most often mutations in the world. In several cases, the definition of mutations had been carried out in the centers of Moscow and St. Petersburg. As a result of the test, the two mutations are defined in 9 children (40,9%), 1 mutation - in 7 (31,8%) and in 6 patients (27,3%) there was no mutation of the CFTR gene identified. In the last group of children the disease is in the mild and medium severity. Cystic fibrosis with pulmonary manifestations have 19 (86,4%) of newly diagnosed children and CF with intestinal manifestations is in 2 (13,6%) cases. In the etiological structure of chronic bronchopulmonary process according to the results of identifications of the microflora of sputum prevails colonization of St.aureus - in 11 children (50%) and Ps. aeruginosae - in (13,6%). The most severe case is a young girl with chronic Pseudomonas infection;
additionally during 1,5 years has Alcaligenes xylosoxidans. Malfunctions of the digestive system in the form of pancreatic insufficiency of the different degree were detected in all the patients. Severe pancreatic insufficiency (elastase of faeces less than 100mkg/g) was revealed in 11 (50%) children, and in 8 of them the content of faeces elastase is from 2 to 10 mkg/g. Insufficiency of the nutritive status is identified in the overwhelming number of children. Chronic protein energy insufficiency of the medium (body weight insufficiency - 22%) - in 1 child and the mild degree (average body weight insufficiency - 14,8%) - in 8 children. 7 children have the body weight insufficiency (average 5.6%). Children are treated by the Protocol of cystic fibrosis, which includes additional power, the appointment of ÑREON, dornase-Alfa, ursodeoxycholic acid, vitamins, courses of antibacterial therapy and cinesiotherapi. It is still the problem with medical maintenance and technical equipment of the medical Department, where the treatment of children with cystic fibrosis is carried out.
90 Problems and achievements in treatment of patients with Cystic Problems and achievements in treatment of patients with Cystic Fibrosis in Russian Federation and abroad Fibrosis in Russian Federation and abroad CystiC Fibrosis in Children oF the leningrad region the CystiC Fibrosis Program (genetiC PeriCuliarities, CliniCal state, in the CF Center oF Verona italy nutritiVe status) Baroukh Maurice Assael Boitsova E.V., Fedotova O.V., Zapevalova O.Y., Ermolaeva E.V. Director Cystic fibrosis center Cystic fibrosis is a severe inherited monogenic pathology, the prevalence of which varies in Verona-Italy different populations. The disease is characterized by variability of the spectrum and severity of clinical manifestations. Diagnosis, treatment and dispensary observation of patients with The CF enter of Verona is one of the largest worldwide and follows over 800 patients. Data cystic fibrosis are underwent treatment in the pulmonary department of children’s regional on the center can be found at the web site www.cfcverona.it.
clinical hospital. In Leningrad region there are 28 patients with cystic fibrosis, 18 children The center follows both pediatric and adult patients. Over the last 20 years there has been a (9 girls - 50%) and 10 adults, upon reaching the age of 18 years in different years they were clear shift in the age range of the patients and nowadays over 55% of the patients are adults. Of transferred under the supervision of physicians. Among of the observed children, 60% (11) these 25% are older than 40 years. Getting older with CF is a clear trend in most countries and are of pre-school age and school-aged are 40% (7 children). In 17 out of 18 cases diagnosed opens new problems such as multiresistant Pseudomonas infections, diabetes, rheumatologic mixed form of the disease, which is confirmed by the low values of elastase - 1. Genetic test disorders, increasing risk of gut cancer. Several patients, however need lung transplantation had been carried out carried out in 17 of the 18 children. The predominant mutation was with a peak around 20-25 years of age. Over 150 patients followed in our center have been F508del, which was revealed in the homozygous state in 6 children, in 7 patients - F508del/0, listed for lung transplantation and near 90 have already been transplanted. In some cases 1 child has F508del/2134insA. In one case the mutation 1677delTA/0 was determined and patients underwent multiorgan transplantation (lung-liver;
in 2 patients the genetic test was negative. The majority of children diagnosed with the However, one should recognize that there is also an increasing number of adults with mild average degree of severity of the disease (14 of 18), in 3 cases mentioned the severe and forms and many patients can now reach adulthood with a good quality of life. Several women in 1 patient - mild. To clarify the status of the respiratory system 14 children were carried have experienced successful pregnancy.
through the computer tomography of the lungs, common bronchiectasis were found in patients, obliterating bronchiolitis in 8 children and in 2 cases minimum changes in the form neonatal screening of thickening of the walls of the bronchial tubes of different caliber were observed. Chronic The CF center of Verona runs since the 1970s a neonatal screening program in the Veneto Ps.Aerug. infection had been diagnosed in 2 children, transitory identification of Ps. Aerug. - in Region. Over 95% of our patients in the last 20 years have been diagnosed after neonatal 2 patients, St. aureus have 13 children, planting H. inf - have 1 child and pathogenic flora was screening. This allows early recognition of patients at risk and early intervention characterized absent in 2 cases. Hepatomegaly with increased levels of transaminases was noted in 4 out by an aggressive nutritional, chest physiotherapy and antiinfective program. Less than 5% of of 18 children, increase of alkaline phosphatase, as a sign of cholestasis, found in 12 of the the pediatric patients exhibit growth retardation, and over 70% of them are Pseudomonas free children. Nutritional status was evaluated with the help of mass-growth index (MRI). MRI is the reaching adolescence.
ratio of actual body weight (kg)100 to which should body weigh (kg) to the growth and the gender. In Cystic Fibrosis, normal MRI =90%. Value of MRI in the normal range occurred in 11 ePiDeMiology oF cF in the veneto region out of 18 (62%) of the children. In other cases (38%) MRI ranged from 80 to 89%, indicating a The epidemiology of CF has greatly changed in our region. An increasing number of mild low nutritive status. Financial income per person in the family on the average is less than forms of CF are diagnosed, median survival is over 40 years with no gender difference, and the thousand rubles in 16 of the 18 observed patients. Treatment of Cystic Fibrosis in the hospital incidence of the disease is decreasing thanks to the diffusion of the carrier test in the general and in the outpatient setting is high-cost based. In spite of the fact that in recent years there population.
has been significant progress in improving of the quality and life expectancy of the patients, in order to achieve results in the treatment of cystic fibrosis, comparable with the economically research anD Future PersPective developed countries, we need a governmental support.
The CF Center of Verona runs also a clinical research program on new drugs designed to overcome the basic defect, on new antibiotics for Pseudomonas lung infection and 92 Problems and achievements in treatment of patients with Cystic Enteral feeding of patients with cystic fybrosis. Fibrosis in Russian Federation and abroad Problems and solutions. Medical Center Rambam’s experience.
on biomarkers of the disease. A team is also involved in basic research on infection and inflammation and on the role of monocytes/macrophages in the deterioration of lung function.
enteral Feeding oF Patients RECENT PUBLICATIONS with CystiC Fybrosis 1. Castellani C, Picci L, Tamanini A, Girardi P, Rizzotti P, Assael BM. Association between carrier screening and incidence of cystic fibrosis. JAMA. Dec 16;
302(23):2573-9. PubMed PMID: 20009057.
2. Viviani L, Bossi A, Assael BM;
Italian Registry for Cystic Fibrosis Collaborative Group. Absence of a gender gap in survival. An analysis of the Italian Problems and solutions registry for cystic fibrosis in the paediatric age. J Cyst Fibros. 3. Sorio C, Buffelli M, Angiari C, Ettorre M, Johansson J, Vezzalini M, Viviani L, Ricciardi M, Verz G, Assael BM, Melotti P. Defective CFTR expression mediCal Center rambam’s exPerienCe and function are detectable in blood monocytes: development of a new blood test for cystic fibrosis. PLoS One. 2011;
6(7):e22212. Epub 2011 Jul 21. PubMed PMID: 21811577;
4. Bergamini G, Di Silvestre D, Mauri P, Cigana C, Bragonzi A, De Palma A, Benazzi L, Dring G, Assael BM, Melotti P, Sorio C. MudPIT analysis of Anna Teleshov, Giezel Diab, Galit livnat, Orly Eshach Adiv, Lior Yaniv, Sandra Arad, Eynav Manor, Lea Bentur released proteins in Pseudomonas aeruginosa laboratory and clinical strains in relation to pro-inflammatory effects. Integr Biol (Camb). 2012 Mar;
Epub 2012 Feb 1. PubMed PMID: Pediatric Pulmonary Unit and Cystic Fibrosis Center, Meyer Children’s Hospital, Rambam Health Care Campus, The Bruce Rappaport Faculty of Medicine, Technion– Israel Institute of Technology, Haifa, Israel introDuction Cystic fibrosis is a systemic hereditary disease caused by mutation of the transmembrane regulator gene (ÌÂÒÐ/CFTR). Most of patients with CF (85%) are carriers of mutations, with such clinical presentations as insufficiency of pancreas. According to recommendations of International CF Association of the year 2005 patient has to maintain body-weight index higher than the 50-th percentile in accordance with survival rates.
Generally accepted indications for gastrostoma in our center are the following conditions:
in case when peroral food additives don’t take effect in weight growth and also deconditioning is seen. Gastrostoma is represented as a positive decision for parents and patients, and as a maintaining therapy to increase their quality of life, lung function and median life duration, but not as a menacing step.
It is proved that enteral feeding in patients with cystic fibrosis:
• increases nutritional status • stabilizes lung function • is more effective as an early interference • less effective when spirometry rates are low.
94 Enteral feeding of patients with cystic fybrosis. Enteral feeding of patients with cystic fybrosis. Problems and solutions. Medical Center Rambam’s experience. Problems and solutions. Medical Center Rambam’s experience.
0,97±0,67 correspondingly (ð=0,011) and «Pain» - 0,96±0,06 and 0,88±0,16 correspondingly (ð=0,008) – in the system Mark 3, also on the attributes «Liveliness» - 1,0±0,0 and 0,98±0, correspondingly (ð=0,011) and «Emotions» 0,94±0,07 and 0,88±0,15 correspondingly (ð=0,024) – in the system Mark 2. Multi-attributed indexes in the systems Mark 3 and Mark in general group were evaluated, and are 0,82 è 0,86 respectively. In comparison of the multi utilitarian indexes in Children with CF attributed indexes in patients with severe and mid-severe course of the disease there were found reliable differences in both systems: 0,90±0,14 and 0,75±0,26, ð=0,008 – in the system Mark 3, and also 0,92±0,12 and 0,83±0,16 ð=0,017 – in the system Mark 2.
I. Vinyarskaya, O. Simonova, V. Chernikov, Y. Gorinova, M. Samsonova, N. Ustinova.
conclusion «Scientifical center of children’s health» RAMN, Moscow Obtained data will be used for making the Russian Utilitarian indexes in children with different conditions database;
for further study of quality of life in children with chronic suMMary diseases;
for evaluation of the QALY rate for the purpose of analysis «cost-effectiveness».
To evaluate the utilitarian indexes used in analysis «cost-usefulness» different standard questionnaires are used. These questionnaires are various in their structure, and differ from usual means of evaluation of QL and are named «multi-attributed measures of usefulness».
Before now, in Russia there were no translated and adapted tools for counting of utilitarian indexes. Laboratory of problems for medical provision and children’s population quality of life ÔÃÁÓ «ÍÖÇÄ» ÐÀÌÍ had translated, adapted and validated the questionnaire Health Utilities Index® (D.H. Feeny, W.J. Furlong, G.W. Torrance, Dundas ON, Canada) versions HUI23P2RU.15Q and HUI23S2RU.15Q.
MethoDs anD Materials During the study, translation and linguistic validation of the questionnaire HUI version15Q were made. It consists of 15 questions and includes two versions: Self-assessment (version for self-assessment for children aged 12 and older) and Proxy-assessment (version for children aged 5 and older, questioning of the child’s representatives). Questionnaire evaluates information for the last 2 weeks. Both versions consist of ñîñòîÿò ranging systems Mark 2 and Mark 3 (HUI 2 and HUI 3). Ranging system Mark 2 consists of 6 attributes: sensation, mobility, emotions, cognitive functions, self-service and pain. The system Mark 3 is a continuation of HUI 2 and contains 8 attributes: vision, hearing, speech, ability to move, small movements, emotions, cognitive functions and pain. For every attribute levels may vary from 1 (normal functioning) to 5-6 points (severe derangement of functioning). Simultaneously with that, multi-attribute indexes are counted in every system;
further they are used in analysis «cost usefulness».
results anD Discussion There were 65 patients with CF involved in the study, observed in pulmonary department of ÔÃÁÓ «ÍÖÇÄ» ÐÀÌÍ: aged 5 to 12 years – 28 (43,1%) children (self-version) and 37 (56,9%) children aged 12 years and older (proxy-version). Gender distribution was composed from boys (46,2%) and 35 girls (53,8%). By severity of disease children divided in the following way:
32 patients (49,2%) with mid-severe and 33 (50,8%) with severe CF. It was revealed that most of all disorders of functionality (level 3) in children with CF were in attributes «Sense», «Emotions»
and «Pain» - in the system Mark 2, also «Emotions», «Pain» and «Cognitive abilities» - in the system Mark 3. Equally with that, the disease affects less on such functionalities as «Vision», «Hearing», «Sense», «Liveliness». The reliable differences between patients with severe and mid-severe CF were assigned on the following attributes: «Movement abitily» - 1,0±0,0 and 96 Problems and achievements in treatment of patients with Cystic Problems and achievements in treatment of patients with Cystic Fibrosis in Russian Federation and abroad Fibrosis in Russian Federation and abroad An important therapeutic aspect of the cystic fibrosis is the maintenance of the status of the respiratory muscles, which play a significant role in the provision of sufficient ventilation functions.
Chronic pulmonary infection, inflammation and a thick viscous secret cause airway obstruction and delay of devastation of alveoli on exhalation;
 due to this, in patients, delay of the air in the alveoli, leading to an increase in lung volume (hyperinflation of the lungs). The hyperinflation of the lungs oPtimization oF the nebulizer theraPy by using oF has a negative impact on the respiratory muscles, first of all on the diaphragm: it flattens, reduces its radius of curvature, changing the orientation of the fibres in the places of their costal attachment and assistiVe deViCes For the mobilization oF bronChus reduces the apposition zone. This leads to the fact that the mechanical efficiency of the diaphragm is lowered, and namely reduces its ability to generate power to change the volume of the lungs [4;
seCret and training oF resPiratory musCles. This contributes to the malfunctions of the mechanics of breathing - the need to breathe at higher level of lungs increases the elastic load on the inspiratory muscles and increases their need for oxygen. [5;
7] On the background of the progression of the process in the lungs Titova E.L.
increase in energy costs breathing leads to the fact that the respiratory muscles are not able «PARI synergy in medicine», LLC, Moscow to provide the necessary level of ventilation. Training of inspiratory muscles (TIM) can increase the strength and endurance of the respiratory muscles, as well as to restore the balance Inhalation therapy and different physiotherapeutical methods become a part of patient’s between the motor signal to the muscles and the mechanical response of muscle on it.  life immediately after the diagnosis of Cystic Fibrois. The earlier therapy of the respiratory tract Thus, the purpose of the TIM is the improvement of the strength and endurance of the disorders is began, the more favorable not only to forecast the course of the disease, but also respiratory muscles, which has a positive effect on clinical symptoms, physical fitness and more likely the achievement of a satisfactory outcome of therapy. Inhalation therapy includes quality of life of patients with Cystic Fibrosis.
local therapy by bronchodilators, mucolytics, antibiotics, glococorticosteroids [1;
2]. The most Contraindications for the TIM in patients with Cystic Fibrosis are:
important moment in the selection and use of inhalation systems is achievement of maximum • Spontaneous pneumothorax in history;
drug deposition in that part of the respiratory tract, where it is needed. There are number • Heamoptysis;
of methods and constructive decisions of inhalation devices for optimum deposition of the • Combination of CF with severe bronchial asthma;
medicine in certain parts of respiratory tract  table. 1.
• Severe exacerbation of disease.
table 1 Constructive features of the inhalation systems and their effectiveness. In the basis of the training of the respiratory muscles are the same principles as in the Constructive features of devices The effect of the use training of other skeletal muscle: the load, specificity and reversibility.
The low-flux compressor, up to 6 l/min Lowering of the medication loss, improving of the table 2. the algorithm of training of the inspiratory muscles.
adoption of the drug even at low inspiratory flow of the patient.
Parameter Identification Recommendations Interrupter of an air flow Possibility of correct breathing Type of simulator Simulator with adjustable inspiratory resistance or maneuver, convenient to the patient;
sufficient reduce of simulator with threshold load.
The number of training 1-2 training sessions a daydepending on physical Sumultaneous use of the device for Increase of the drug deposition due to stabilization of sessions in a day performance of the patient.
positive expiratory pressure with the the bronchia surface;
improvement of the evacuation of Frequency nebulizer bronchial secretion;
reduce of the treatment time. Number of days per week 5-7 days per week training sessions according to physical abilily of the patient.
Puslating aerosol The delivery of the medication into the poor ventilated parts of respiratory system, such as the nasal cavities. Load which the patient has to The MIP percentage – the most common approach Intensity overcome for the determination of inspiratory load.
Consistent use of the nozzle to the A nozzle for the central part is used forbronchodilators Recommended range – 30-60 % MIP nebulizer for central and peripheral parts and mucolytics, a nozzle for the peripheral part – for an Duration of every session Up to 30 minutes a day depending on the load:
of the respiratory tract. antibiotic and GCS.
high load can not be maintained as long as low.
At the beginning the trainings may be short – 3- Use of compressor nebulisers for patients with Cystic Fibrosis may be preferable by the munites per session.
Duration following reasons: Number of weeks for training More than 6 weeks. After the termination of • High hygienic level. trainings all the measures are returned to original level.
• Low medication loss during inhalation.
• Minimal residual volume. Maximum inspiratory Repeated measures of MIP are needed for Conrtol pressure in the oral cavity correction of the load intensity once a week, or at • A combination of inhalation and physiotherapy.
(MIP) least monthly.
98 Problems and achievements in treatment of patients with Cystic Fibrosis in Russian Federation and abroad äëÿ çàìåòîê / notes During the TIM patients are recommended to keep a diary, because it reminds them of the need to observe the schedule of the training and at the same time gives information about the actual delivery of the training and their aftermath.
table 3. parameters which are to control during training Aim Parameter How to control Revelation of the Blood pressure, frequency of cardiac More details about intolerance for contractions, breathing frequency, respiratory distress physical load other signs of respiratory distress- syndrome syndrome or intolerance for physical load To avoid the fatigue Discoordination of movements of Observation of respiratory the respiratory muscles muscles Shortness of breathing during Observation treatment Complaints on fatigue after the Poll trainins session To avoid an injury Muscle soreness Poll of the muscles Lowering of power Measuring of MIP Lowering of tolerance Failure to maintain the intencity and duration of routine training load To avoid CO2 level at the end of exalation Capnographer hypercapnia Oxygen saturation Pusloximeter Headache or mental confusion Poll LITERATURE 1. Geppe N.A. et al. Inhalation nebulizer therapy of the respiratory tract disorders in children. Moscow 2. Kapranov N.I. Kashirskaya N.Y. Simonova O.I. et al. Cystic Fibrosis: modern achievements and problems: Methodical recommendations- M., 3. Chernyak A. V., Amelina E. L., Chikina S. Y., Krasovsky S. A. Training of the inspiratory muscles in patients with Cystic Fibrosis. Methodical recommendations. M., 4. Davis P.B., Drumm M., Konstan M.W. - Cystic fibrosis (state of the art). Am.J.Respir.Crit.Care Med. 1996. 154: 1229-1256.
5. Bell S.C., Saunders M.J., Elborn J.S., Shale D.J. – 6. Resting energy expenditure and oxygen cost of breathing in patients with cystic fibrosis. Thorax. 1996. 51: 126-131.
7. Geddes E.L., Reid W.D., Brooks D., O’Brien K., Crowe J. - A primer on inspiratory muscle trainers. The buyers’ guide to respiratory care products. 2006. 59-67.
8. Laube et al. J. Allergy Clin. Immunolol. äëÿ çàìåòîê / notes pUblished with the assistanCe:
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