FEATURES OF CLINICAL PRESENTATION AND DIAGNOSIS OF CYSTIC FIBROSIS
Abstract
Cystic fi brosis is a common hereditary disease caused by a mutation of the CFTR gene responsible for the synthesis, preservation of the structure and function of the CFTR protein, manifested primarily by pathology of the gastrointestinal tract and respiratory system. The lack of protein function in cystic fi brosis leads to an increase in the viscosity of the secretion of exocrine glands, obturation of organs and disruption of their functions. As a result, it causes steatorrhea, malabsorption, diabetes mellitus, metabolic disorders, with developmental delay and chronic bronchopulmonary process. This article will consider the main aspects of the clinical course and diagnosis of this disease.
References
Кондратьева E.И., Каширская Н.Ю., Рославце- ва Е.А. Обзор национального консенсуса «Муковисцидоз: определение, диагностические критерии, терапия» для диетологов и гастроэнтерологов. Вопросы детской диетологии. 2018; 16(1). С. 58–74.
López-Valdez J.A., Aguilar-Alonso L.A., Gándara- Quezada V. et al. Cystic fibrosis: current concepts. Bol Med Hosp Infant Mex. 2021;78(6). Р. 584-596. DOI: 10.24875/BMHIM.20000372.
Регистр пациентов с муковисцидозом в Рос- сийской Федерации. 2020 год. / Под редакцией Е.И. Кондратьевой, С.А. Красовского, М.А. Стари- новой и др. М.: МЕДПРАКТИКА-М; 2022. С. 68.
De Boeck K. Cystic fibrosis in the year 2020: disease with a new face. Acta Paediatr. 2020;109(5). Р. 893– 899. DOI: https://doi.org/10.1111/apa.15155.
Lopes-Pacheco M. CFTR modulators: Shedding light on precision medicine for cystic fibrosis. Front Pharmacol. 2016;7. Р.275. DOI: https://doi. org/10.3389/fphar.2016.00275.
Капранов Н.И., Каширская Н.Ю. Муковисцидоз. М.: МЕДПРАКТИКА-М; 2014. С. 672.
Mogayzel P.J., Naureckas E.T., Robinson K.A. Cystic Fibrosis Pulmonary Guidelines. Am J Respir Crit Care Med. 2013;187(7):680–689. DOI: https://doi. org/10.1164/rccm.201207-1160oe.
Национальный консенсус «Муковисцидоз: опре- деление, диагностические критерии, терапия» / под ред. Е.И. Кондратьевой, Н.Ю. Каширской, Н.И. Капранова. М.: ООО «Компания БОРГЕС»; 2016. С. 205.
Demco C.A., Stern R.C., Doershuk C.F. Stenotrophomonas maltophilia in cystic fibrosis: incidence and prevalence. Pediatr Pulmonol. 1998;25(5):304–308. DOI: https://doi.org/10.1002/ (sici)1099-0496(199805)25:53.0.co;2-i.
Denning D.W., Cadranel J., Beigelman-Aubry C. et al. Chronic pulmonary aspergillosis: rationale and clinical guidelines for 188 diagnosis and management. Eur Respir J. 2016;47(1):45–68. DOI: https://doi.org/10.1183/13993003.00583-2015.
Kosmidis C., Denning D.W. The clinical spectrum of pulmonaryaspergillosis. Thorax. 2015;70(3):270–277. DOI: https://doi.org/10.1136/thoraxjnl-2014-206291.
Шагинян И.А., Капранов Н.И., Чернуха М.Ю. и др. Микробный пейзаж нижних дыхательных путей у различных возрастных групп детей, больных муковисцидозом. Журнал микробиологии, эпидемиологии и иммунобиологии. 2010. № 1. С. 15– 20.
Burke M.S., Ragi J.M., Karamanoukian H.L. et al. New strategies in thenon-operative management of meconium ileus. J Pediat Surg. 2002;37(5):760– 764. DOI: https://doi.org/10.1053/jpsu.2002.32272.
Кондратьева Е.И., Шерман В.Д., Амелина Е.Л. и др. Клинико-генетическая характеристика и исходы мекониевого илеуса при муковисцидозе. Российский вестник перинаталогии и педиатрии. 2016. Т. 61. № 6. С. 77–81. DOI: https://doi. org/10.21508/1027-4065-2016-6-77-81.
Debray D., Narkewicz M.R., Bodewes F.A. et al. Cystic Fibrosis-related Liver Disease: Research Challenges and Future Perspectives. J Pediatr Gastroenterol Nutr. 2017;65(4):443–448. DOI: https://doi. org/10.1097/MPG.0000000000001676.
Ciucă I.M., Pop L., Tămaş L. et al. Cystic fibrosis liver disease-from diagnosis to risk factors. Rom J Morphol Embryol. 2014;55(1). Р. 91–95.
Klotter V., Gunchick C., Siemers E. et al. Assessment of pathologic increase in liver stiffness enables earlier diagnosis of CFLD: Results from a prospective longitudinal cohort study. PloS One. 2017;12(6):e0178784. DOI: https://doi.org/10.1371/ journal.pone.0178784.
Terliesner N., Vogel M., Steighardt A. et al. Cystic- fibrosis related-diabetes (CFRD) is preceded by and associated with growth failure and deteriorating lung function. J Pediatr Endocrinol Metab. 2017;30(8):815– 821. DOI: https://doi.org/10.1515/ jpem-2017-0005.
Edenborough FP. Women with cystic fibrosis and their potential for reproduction. Thorax. 2001;56(8):649–655. DOI: https://doi.org/10.1136/ thorax.56.8.649.
Амелина Е.Л., Красовский С.А., Шугинин И.О. Муковисцидоз и беременность: клинико-генетические, функциональные и микробиологические характеристики пациенток. Педиатрия. Журнал им. Г.Н. Сперанского. 2014. Т. 93. № 4. С. 38–43.
Aris R.M., Merkel P.A., Bachrach L.K. et al. Consensus statement: Guide to bone health and disease in cystic fibrosis. J Clin Endocrinol Metab. 2005;90(3):1888–1896. DOI: https://doi.org/10.1210/ jc.2004-1629.
Климко Н.Н. Микозы: диагностика и лечение: ру- ководство для врачей. 3-е изд., перераб. и доп. М.: Фармтек; 2017. С. 272.
Орлов А. В., Симонова О. И., Рославцева Е. А., Шадрин Д.И. Муковисцидоз (клиническая картина, диагностика, лечение, реабилитация, диспансеризация): учебное пособие для врачей. СПб.: Изд-во СЗГМУ им. И. И. Мечникова, 2014. С. 160.
Castellani C., Duff A.J.A., Bell S.C. et al. ECFS best practice guidelines: the 2018 revision. J Cyst Fibros. 2018;17(2).Р.153–178. DOI: https://doi.org/10.1016/j. jcf.2018.02.006.
Stevens D.A., Moss R.B., Kurup V.P. et al. Allergic bronchopulmonary aspergillosis in cystic fibrosis — state of the art: Cystic Fibrosis Foundation Consensus Conference. Clin Infect Dis. 2003;37(Suppl 3). Р.S225–S264. DOI: https://doi. org/10.1086/376525.
Liu J.C., Modha D.E., Gaillard E.A. What is the clinical significance of filamentous fungi positive sputum cultures in patients with cystic fibrosis? J Cyst Fibros. 2013;12(3). Р.187–193. DOI: https://doi.org/10.1016/j. jcf.2013.02.003.
Geller D.E., Kaplowitz H., Light M.J., Colin A.A. Allergic bronchopulmonary aspergillosis in cystic fibrosis: reported prevalence, regional distribution, and patient characteristics. Scientific Advisory Group, Investigators, and Coordinators of the Epidemiologic Study of Cystic Fibrosis. Chest. 1999;116(3). Р.639–646. DOI: https://doi.org/10.1378/ chest.116.3.639.
Zolin A., Orenti A., van Rens J. et al. ECFS Patient Registry. Annual Data Report (2017 data). Version 1.2019. Available online: https://www.ecfs.eu/ sites/default/files/general- content- images/ workinggroups/ecfs-patient-registry/ECFSPR_ Report2017_v1.3.pdf. Accessed on April 17, 2022.
Leung D.H., Narkewicz M.R. Cystic Fibrosis-related cirrhosis. J Cyst Fibros. 2017;16(Suppl 2). Р.50–S61. DOI: https://doi.org/10.1016/j.jcf.2017.07.002.
Pseudo-Bartter’s syndrome. In: Clinical Guidelines: Care of Children with Cystic Fibrosis. Royal Brompton Hospital; 2020. Vol. 8. P. 173–174.
Akata D., Akhan O. Liver manifestations of cystic fibrosis. Eur J Radiol. 2007;61(1).Р.11–17. DOI: https:// doi.org/10.1016/j.ejrad.2006.11.008.
Williams S.M., Goodman R., Thomson A. et al. Ultrasound evaluation of liver disease in cystic fibrosis as part of an annual assessment clinic: a 9-year review. Clin Radiol. 2002;57(5).Р.365–370. DOI: https://doi.org/10.1053/crad.2001.0861.
Mueller-Abt P.R., Frawley K.J., Greer R.M. et al. Comparison of ultrasound and biopsy findings in children with cystic fibrosis related liver disease. J Cyst Fibros. 2008;7(3).Р.215–221. DOI: https://doi. org/10.1016/j.jcf.2007.08.001.
Durand F., Valla D. Assessment of the prognosis of cirrhosis: Child-Pugh versus MELD. J Hepatol. 2005;42(Suppl 1).Р.100–S107. DOI: https://doi. org/10.1016/j.jhep.2004.11.015.
Moran A., Brunzell C., Cohen R.C. Clinical care guidelines for cystic fibrosis-related diabetes: a position statement of the American Diabetes Association and a clinical practice guideline of the Cystic Fibrosis Foundation, endorsed by the Pediatric Endocrine Society. Diabetes Care. 2010;33(12). Р.2697–2708. DOI: https://doi.org/10.2337/dc10-1768.
Gordon C.M., Leonard M.B., Zemel B.S. 2013 Pediatric Position Development Conference: Executive Summary and Reflections. J Clin Densitom. 2014;17(2).Р.219–224. DOI: https://doi. org/10.1016/j.jocd.2014.01.007.
Richards S., Aziz N., Bale S. et al. Rehm, the ACMG Laboratory Quality Assurance Committee Standardsand guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5).Р.405–424. DOI: http://doi.org/10.1038/gim.2015.30.
Turck D., Braegger C.P., Colombo C. et al. ESPEN- ESPGHANECFS guidelines on nutrition care for infants, children, and adults with cystic fibrosis. Clin Nutr. 2016;35(3).Р.557–577. DOI: http://doi. org/10.1016/j.clnu.2016.03.004.
Leifke E., Friemert M., Heilmann M. et al. Sex steroid sand body composition in men with cystic fibrosis. Eur J Endocrinol. 2003;148(5).Р.551–557. DOI: https:// doi.org/10.1530/eje.0.1480551.
Blackman S.M., Tangpricha V. Endocrine Disordersin Cystic Fibrosis. Pediatr Clin North Am. 2016;63(4).Р.699–708. DOI: https://doi.org/10.1016/j. pcl.2016.04.009.
Kang S.H., Dalcin P.T.R., Piltcher O.B, Migliavacca R.O. Chronic rhinosinusitis and nasal polyposis in cystic fibrosis: update on diagnosis and treatment. J Bras Pneumol. 2015;41(1).Р.65–76. DOI: https://doi. org/10.1590/S1806-37132015000100009.
Исаков Ю.Ф., Дронова А.Ф. Детская хирургия: национальное руководство. М.: ГЭОТАР-Медиа; 2009. С. 328–331.
REFERENCES
Kondrat'eva E.I., Kashirskaya N.Yu., Roslavtseva E.A. Obzor natsional'nogo konsensusa «Mukovistsidoz: opredelenie, diagnosticheskie kriterii, terapiya» dlya dietologov i gastroenterologov [Review of national consensus "Mukovistsidoz: definition, dia- gnostic criteria, therapy" for nutritionists and gastroenterologists]. Voprosy detskoy dietologii. 2018; 16(1). S. 58–74. (in Russian).
López-Valdez J.A., Aguilar-Alonso L.A., Gándara-Quezada V. et al. Cystic fibrosis: current concepts. Bol Med Hosp Infant Mex. 2021;78(6). R. 584-596. DOI: 10.24875/BMHIM.20000372.
Registr patsientov s mukovistsidozom v Rossiyskoy Federatsii [Register of cystic fibrosis patients in the Russian Federation]. 2020 god. /Pod redaktsiey E.I. Kondrat'evoy, S.A. Krasovskogo, M.A. Starinovoy i dr. M.: MEDPRAKTIKA-M, 2022, S. 68. (in Russian).
De Boeck K. Cystic fibrosis in the year 2020: disease with a new face. Acta Paediatr. 2020;109(5). P. 893– 899. DOI: https://doi.org/10.1111/apa.15155.
Lopes-Pacheco M. CFTR modulators: Shedding light on precision medicine for cystic fibrosis. Front Phar- macol. 2016;7. S. 275. DOI: https://doi.org/10.3389/ fphar.2016.00275.
Kapranov N.I., Kashirskaya N.Yu. Mukovistsidoz [Cystic fibrosis]. M.: MEDPRAKTIKA-M; 2014. S. 672. (in Russian).
Mogayzel P.J., Naureckas E.T., Robinson K.A. Cyst- ic Fibrosis Pulmonary Guidelines. Am J Respir Crit Care Med. 2013;187(7):680–689. DOI: https://doi. org/10.1164/rccm.201207-1160oe.
Natsional'nyy konsensus «Mukovistsidoz: opre- delenie, diagnosticheskie kriterii, terapiya» [Natio- nal Consensus Cystic Fibrosis: Definition, Diagnos- tic Criteria, Therapy] / pod red. E.I. Kondrat'evoy, N.Yu. Kashirskoy, N.I. Kapranova. M.: OOO «Kom- paniya BORGES»; 2016. S. 205. (in Russian).
Demco C.A., Stern R.C., Doershuk C.F. Stenotro- phomonas maltophilia in cystic fibrosis: incidence and prevalence. Pediatr Pulmonol. 1998;25(5):304– 308. DOI: https://doi.org/10.1002/ (sici)1099- 0496(199805)25:53.0.co;2-i.
Denning D.W., Cadranel J., Beigelman-Aubry C. et al. Chronic pulmonary aspergillosis: rationale and clinical guidelines for 188 diagnosis and management. Eur Respir J. 2016;47(1):45–68. DOI: https://doi.org/10.1183/13993003.00583-2015.
Kosmidis C., Denning D.W. The clinical spectrum of pulmonary aspergillosis. Thorax. 2015;70(3):270–277. DOI: https://doi.org/10.1136/thorax- jnl-2014-206291.
Shaginyan I.A., Kapranov N.I., Chernukha M.Yu. i dr. Mikrobnyy peyzazh nizhnikh dykhatel'nykh putey u razlichnykh vozrastnykh grupp detey, bol'nykh mukovistsidozom [Microbic landscape of the lower airways at various age groups of children, patients mukovistsidozy]. Zhurnal mikrobiologii, epide- miologii i immunobiologii. 2010. № 1. S. 15–20. (in Russian).
Burke M.S., Ragi J.M., Karamanoukian H.L. et al. New strategies in thenon-operative management of meconium ileus. J Pediat Surg. 2002;37(5):760– 764. DOI: https://doi.org/10.1053/jpsu.2002.32272.
Kondrat'eva E.I., Sherman V.D., Amelina E.L. i dr. Kliniko-geneticheskaya kharakteristika i iskhody mekonievogo ileusa pri mukovistsidoze [Clinical genetic characteristics and outcomes of meconium ileus in cystic fibrosis]. Rossiyskiy vestnik peri- natalogii i pediatrii. 2016. T. 61. № 6. S. 77–81. DOI: https://doi.org/10.21508/1027-4065-2016-6-77-81. (in Russian).
Debray D., Narkewicz M.R., Bodewes F.A. et al. Cys- tic Fibrosis-related Liver Disease: Research Challenges and Future Perspectives. J Pediatr Gastro- enterol Nutr. 2017;65(4):443–448. DOI: https://doi. org/10.1097/MPG.0000000000001676.
Ciucă I.M., Pop L., Tămaş L. et al. Cystic fibrosis liver disease-from diagnosis to risk factors. Rom J Morphol Embryol. 2014;55(1). R.91–95.
Klotter V., Gunchick C., Siemers E. et al. Assess- ment of pathologic increase in liver stiffness enables earlier diagnosis of CFLD: Results from a prospective longitudinal cohort study. PloS One.2017;12(6):e0178784. DOI: https://doi.org/10.1371/ journal.pone.0178784.
Terliesner N., Vogel M., Steighardt A. et al. Cystic- fibrosis related-diabetes (CFRD) is preceded by and associated with growth failure and deterio- rating lung function. J Pediatr Endocrinol Metab. 2017;30(8):815– 821. DOI: https://doi.org/10.1515/ jpem-2017-0005.
Edenborough FP. Women with cystic fibrosis and their potential for reproduction. Thorax. 2001;56(8):649–655. DOI: https://doi.org/10.1136/ thorax.56.8.649.
Amelina E.L., Krasovskiy S.A., Shuginin I.O. Muko- vistsidoz i beremennost': kliniko-geneticheskie, funktsional'nye i mikrobiologicheskie kharakte- ristiki patsientok [Mukovistsidoz and pregnancy: kliniko-genetic, functional and microbiological characteristics of patients]. Pediatriya. Zhurnal im.G.N. Speranskogo. 2014. T. 93. № 4. S. 38–43. (in Russian).
Aris R.M., Merkel P.A., Bachrach L.K. et al. Consensus statement: Guide to bone health and disease in cystic fibrosis. J Clin Endocrinol Metab. 2005;90(3):1888–1896. DOI: https://doi.org/10.1210/ jc.2004-1629.
Klimko N.N. Mikozy: diagnostika i lechenie: rukovodstvo dlya vrachey [Mycoses: diagnostics and treatment: the management for doctors]. 3-e izd., pererab. i dop. M.: Farmtek; 2017. S.272. (in Russian).
Orlov A.V., Simonova O.I., Roslavtseva E.A., Shad- rin D.I. Mukovistsidoz (klinicheskaya kartina, diagnostika, lechenie, reabilitatsiya, dispanserizatsiya): uchebnoe posobie dlya vrachey [Mukovistsidoz (clinical picture, diagnostics, treatment, rehabili- tation, medical examination): manual for doctors]. SPb.: Izd-vo SZGMU im. I. I. Mechnikova, 2014. S.160. (in Russian).
Castellani C., Duff A.J.A., Bell S.C. et al. ECFS best practice guidelines: the 2018 revision. J Cyst Fibros. 2018;17(2). P. 153–178. DOI: https://doi.org/10.1016/j. jcf.2018.02.006.
Stevens D.A., Moss R.B., Kurup V.P. et al. Allergic bronchopulmonary aspergillosis in cystic fibrosis — state of the art: Cystic Fibrosis Foundation Consen- sus Conference. Clin Infect Dis. 2003;37(Suppl 3). R.S225–S264. DOI: https://doi.org/10.1086/376525.
Liu J.C., Modha D.E., Gaillard E.A. What is the cli- nical significance of filamentous fungi positive sputum cultures in patients with cystic fibrosis? J Cyst Fibros. 2013;12(3). P. 187–193. DOI: https://doi. org/10.1016/j.jcf.2013.02.003.
Geller D.E., Kaplowitz H., Light M.J., Colin A.A. Aller- gic bronchopulmonary aspergillosis in cystic fibrosis: reported prevalence, regional distribution, and patient characteristics. Scientific Advisory Group, In vestigators, and Coordinators of the Epidemiologic Study of Cystic Fibrosis. Chest. 1999;116(3). P. 639– 646. DOI: https://doi.org/10.1378/chest.116.3.639.
Zolin A., Orenti A., van Rens J. et al. ECFS Patient Registry. Annual Data Report (2017 data). Version 1.2019. Available online: https:// www.ecfs.eu/sites/ default/files/general-content-images/working- groups/ecfs-patient-registry/ECFSPR_Report2017_ v1.3.pdf. Accessed on April 17, 2022.
Leung D.H., Narkewicz M.R. Cystic Fibrosis-related cirrhosis. J Cyst Fibros. 2017;16(Suppl 2). P. 50–S61. DOI: https://doi.org/10.1016/j.jcf.2017.07.002.
Pseudo-Bartter’s syndrome. In: Clinical Guidelines: Care of Children with Cystic Fibrosis. Royal Brompton Hospital; 2020. Vol.8. P. 173–174.
Akata D., Akhan O. Liver manifestations of cystic fi- brosis. Eur J Radiol. 2007;61(1). P. 11–17. DOI: https:// doi.org/10.1016/j.ejrad.2006.11.008.
Williams S.M., Goodman R., Thomson A. et al. Ultra- sound evaluation of liver disease in cystic fibrosis as part of an annual assessment clinic: a 9-year review. Clin Radiol. 2002;57(5). P. 365–370. DOI: https://doi. org/10.1053/crad.2001.0861.
Mueller-Abt P.R., Frawley K.J., Greer R.M. et al. Comparison of ultrasound and biopsy findings in children with cystic fibrosis related liver disease. J Cyst Fibros. 2008;7(3). P. 215–221. DOI: https://doi. org/10.1016/j.jcf.2007.08.001.
Durand F., Valla D. Assessment of the prognosis of cirrhosis: Child-Pugh versus MELD. J Hepatol. 2005;42(Suppl 1). P. 100–S107. DOI: https://doi. org/10.1016/j.jhep.2004.11.015.
Moran A., Brunzell C., Cohen R.C. Clinical care guidelines for cystic fibrosis-related diabetes: a position statement of the American Diabetes Associ- ation and a clinical practice guideline of the Cystic Fibrosis Foundation, endorsed by the Pediatric Endocrine Society. Diabetes Care. 2010;33(12). P. 2697– 2708. DOI: https://doi.org/10.2337/dc10-1768.
Gordon C.M., Leonard M.B., Zemel B.S. 2013 Pedi- atric Position Development Conference: Executive Summary and Reflections. J Clin Densitom. 2014;17(2). P. 219–224. DOI: https://doi.org/10.1016/j. jocd.2014.01.007.
Richards S., Aziz N., Bale S. et al. Rehm, the ACMG Laboratory Quality Assurance Committee Stan dards and guidelines for the interpretation of se- quence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5). P. 405–424. DOI: http://doi.org/10.1038/gim.2015.30.
Turck D., Braegger C.P., Colombo C. et al. ESPEN- ESPGHANECFS guidelines on nutrition care for infants, children, and adults with cystic fibrosis. Clin Nutr. 2016;35(3). P. 557–577. DOI: http://doi. org/10.1016/j.clnu.2016.03.004.
Leifke E., Friemert M., Heilmann M. et al. Sex steroid sand body composition in men with cystic fibro- sis. Eur J Endocrinol. 2003;148(5). P. 551–557. DOI: https://doi.org/10.1530/eje.0.1480551.
Blackman S.M., Tangpricha V. Endocrine Disor- dersin Cystic Fibrosis. Pediatr Clin North Am. 2016;63(4). P. 699–708. DOI: https://doi.org/10.1016/j. pcl.2016.04.009.
Kang S.H., Dalcin P.T.R., Piltcher O.B, Migliavacca R.O. Chronic rhinosinusitis and nasal polyposis in cystic fibrosis: update on diagnosis and treatment. J Bras Pneumol. 2015;41(1). P. 65–76. DOI: https://doi. org/10.1590/S1806-37132015000100009.
Isakov Yu.F., Dronova A.F. Detskaya khirurgiya: natsio- nal'noe rukovodstvo [Children's surgery: national lea- ders]. M.: GEOTAR-Media; 2009. S. 328–331. (in Russian).
