Pediatr Gastroenterol Hepatol Nutr.  2018 Oct;21(4):306-314. 10.5223/pghn.2018.21.4.306.

Cystic Fibrosis: Clinical Phenotypes in Children and Adolescents

• dos Santos ALM
• de Melo Santos H
• Nogueira M
• Távora HT
• de Lourdes Jaborandy Paim da Cun C
• de Melo Seixas RBP
• de Freitas Velloso Monte L
• de Carvalho E

• KMID: 2421993
• DOI: http://doi.org/10.5223/pghn.2018.21.4.306

Abstract

PURPOSE
The objective of this study was to describe the clinical phenotypes of children and adolescents with cystic fibrosis (CF); and to assess the role of pancreatic insufficiency and neonatal screening in diagnosis.
METHODS
A cross-sectional study was conducted, which included 77 patients attending a reference center of CF between 2014 and 2016. Epidemiological data, anthropometric measurements, and the presence of pulmonary, pancreatic, gastrointestinal and hepatobiliary manifestations were evaluated based on clinical data and complementary examinations.
RESULTS
Of the 77 patients, 51.9% were male, with a median age of 147 months (7.0-297.0 months), and the majority showed adequate nutritional status. The most common phenotype was pulmonary (92.2%), followed by pancreatic (87.0%), with pancreatic insufficiency in most cases. Gastrointestinal manifestation occurred in 46.8%, with constipation being the more common factor. Hepatobiliary disease occurred in 62.3% of patients. The group with pancreatic insufficiency was diagnosed earlier (5.0 months) when compared to the group with sufficiency (84.0 months) (p=0.01). The age of diagnosis was reduced following implementation of neonatal screening protocols for CF (6.0 months before vs. 3.0 months after, p=0.02).
CONCLUSION
The pulmonary phenotype was the most common, although extrapulmonary manifestations were frequent and clinically relevant, and should mandate early detection and treatment. Neonatal screening for CF led to earlier diagnosis in patients with pancreatic failure, and therefore, should be adopted universally.

Keyword

Cystic fibrosis; Neonatal screening; Exocrine pancreatic insufficiency; Gastrointestinal diseases; Liver diseases

MeSH Terms

Adolescent*
Child*
Constipation
Cross-Sectional Studies
Cystic Fibrosis*
Diagnosis
Exocrine Pancreatic Insufficiency
Gastrointestinal Diseases
Humans
Infant, Newborn
Liver Diseases
Male
Neonatal Screening
Nutritional Status
Phenotype*

Reference

1. Kelly T, Buxbaum J. Gastrointestinal manifestations of cystic fibrosis. Dig Dis Sci. 2015; 60:1903–1913.

2. Gelfond D, Borowitz D. Gastrointestinal complications of cystic fibrosis. Clin Gastroenterol Hepatol. 2013; 11:333–342.

3. Carvalho E, Ferreira CT, Silva LR. Gastroenterologia e nutrição em pediatria. Barueri: Manole;2012.

4. Sathe MN, Freeman AJ. Gastrointestinal, pancreatic, and hepatobiliary manifestations of cystic fibrosis. Pediatr Clin North Am. 2016; 63:679–698.

5. Hurley MN, McKeever TM, Prayle AP, Fogarty AW, Smyth AR. Rate of improvement of CF life expectancy exceeds that of general population--observational death registration study. J Cyst Fibros. 2014; 13:410–415.

6. Farrell PM, Rosenstein BJ, White TB, Accurso FJ, Castellani C, Cutting GR, et al. Guidelines for diagnosis of cystic fibrosis in newborns through older adults: Cystic Fibrosis Foundation consensus report. J Pediatr. 2008; 153:S4–S14.

7. World Health Organization. The WHO child growth standards, 2006 [Internet]. Geneva: WHO;2006. cited 2017 Jan 31. Available from: http://www.who.int/childgrowth/en/.

8. Pereira CAC. Espirometria. J Pneumol. 2002; 28:Suppl 3. S1–S82.

9. Lee TW, Brownlee KG, Conway SP, Denton M, Littlewood JM. Evaluation of a new definition for chronic Pseudomonas aeruginosa infection in cystic fibrosis patients. J Cyst Fibros. 2003; 2:29–34.

10. Moran A, Brunzell C, Cohen RC, Katz M, Marshall BC, Onady G, et al. 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; 33:2697–2708.

11. Witt H, Apte MV, Keim V, Wilson JS. Chronic pancreatitis: challenges and advances in pathogenesis, genetics, diagnosis, and therapy. Gastroenterology. 2007; 132:1557–1573.

12. Vandenplas Y, Rudolph CD, Di Lorenzo C, Hassall E, Liptak G, Mazur L, et al. Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr Gastroenterol Nutr. 2009; 49:498–547.

13. Ciucă IM, Pop L, Tămaş L, Tăban S. Cystic fibrosis liver disease - from diagnosis to risk factors. Rom J Morphol Embryol. 2014; 55:91–95.

14. Registro Brasileiro de Fibrose cística [Internet]. São Paulo: Grupo Brasileiro de Estudos de Fibrose Cística;2014. cited 2017 Dec 10. Available from: http://portalgbefc.org.br/wp-content/uploads/2016/11/Registro2014_v09.pdf.

15. Cystic Fibrosis Foundation Patient Registry. 2012 annual data report to the center directors [Internet]. Bethesda: Cystic Fibrosis Foundation;2012. cited 2017 Jan 20. Available from: https://www.cff.org/.

16. Yadav K, Singh M, Angurana SK, Attri SV, Sharma G, Tageja M, et al. Evaluation of micronutrient profile of North Indian children with cystic fibrosis: a case-control study. Pediatr Res. 2014; 75:762–766.

17. Rizzo LC, Fischer GB, Maróstica PJ, Mocelin HT. Profile of cystic fibrosis in two reference centers in southern Brazil. Rev Assoc Med Bras (1992). 2015; 61:150–155.

18. Del Ciampo IR, Del Ciampo LA, Sawamura R, de Oliveira LR, Fernandes MI. Nutritional status of adolescents with cystic fibrosis treated at a reference center in the southeast region of Brazil. Ital J Pediatr. 2015; 41:51.

19. Goss CH, Muhlebach MS. Review: Staphylococcus aureus and MRSA in cystic fibrosis. J Cyst Fibros. 2011; 10:298–306.

20. Elborn JS. Cystic fibrosis. Lancet. 2016; 388:2519–2531.

21. Simmonds NJ. Cystic fibrosis in the 21st century. Respir Med. 2010; 24:85–96.

22. Munck A, Alberti C, Colombo C, Kashirskaya N, Ellemunter H, Fotoulaki M, et al. International prospective study of distal intestinal obstruction syndrome in cystic fibrosis: Associated factors and outcome. J Cyst Fibros. 2016; 15:531–539.

23. Robinson NB, DiMango E. Prevalence of gastroesophageal reflux in cystic fibrosis and implications for lung disease. Ann Am Thorac Soc. 2014; 11:964–968.

24. Mousa HM, Woodley FW. Gastroesophageal reflux in cystic fibrosis: current understandings of mechanisms and management. Curr Gastroenterol Rep. 2012; 14:226–235.

25. Gorter RR, Karimi A, Sleeboom C, Kneepkens CM, Heij HA. Clinical and genetic characteristics of meconium ileus in newborns with and without cystic fibrosis. J Pediatr Gastroenterol Nutr. 2010; 50:569–572.

26. El-Chammas KI, Rumman N, Goh VL, Quintero D, Goday PS. Rectal prolapse and cystic fibrosis. J Pediatr Gastroenterol Nutr. 2015; 60:110–112.

27. Ramos AF, de Fuccio MB, Moretzsohn LD, Barbosa AJ, Passos Mdo C, Carvalho RS, et al. Cystic fibrosis, gastroduodenal inflammation, duodenal ulcer, and H. pylori infection: the "cystic fibrosis paradox" revisited. J Cyst Fibros. 2013; 12:377–383.

28. Salvatore D, Buzzetti R, Mastella G. Update of literature from cystic fibrosis registries 2012-2015. Part 6: Epidemiology, nutrition and complications. Pediatr Pulmonol. 2017; 52:390–398.

29. Nascimento FS, Sena NA, Ferreira TDA, Marques CDF, Silva LR, Souza EL. Hepatobiliary disease in children and adolescents with cystic fibrosis. J Pediatr (Rio J). 2017; DOI: 10.1016/j.jped.2017.07.006. [In press].

30. Leeuwen L, Fitzgerald DA, Gaskin KJ. Liver disease in cystic fibrosis. Paediatr Respir Rev. 2014; 15:69–74.

31. Kobelska-Dubiel N, Klincewicz B, Cichy W. Liver disease in cystic fibrosis. Prz Gastroenterol. 2014; 9:136–141.

32. Eminoglu TF, Polat E, Gökçe S, Ezgü FS, Senel S, Apaydin S. Cystic fibrosis presenting with neonatal cholestasis simulating biliary atresia in a patient with a novel mutation. Indian J Pediatr. 2013; 80:502–504.

33. Flass T, Narkewicz MR. Cirrhosis and other liver disease in cystic fibrosis. J Cyst Fibros. 2013; 12:116–124.

34. Witters P, Libbrecht L, Roskams T, Boeck KD, Dupont L, Proesmans M, et al. Noncirrhotic presinusoidal portal hypertension is common in cystic fibrosis-associated liver disease. Hepatology. 2011; 53:1064–1065.

35. Witters P, De Boeck K, Dupont L, Proesmans M, Vermeulen F, Servaes R, et al. Non-invasive liver elastography (Fibroscan) for detection of cystic fibrosis-associated liver disease. J Cyst Fibros. 2009; 8:392–399.