Helping patients with cystic fibrosis live longer

,

Applied Evidence

Helping patients with cystic fibrosis live longer

J Fam Pract. 2016 March;65(3):188-194

By

Douglas Lewis, MD, FAAFP

Lung and pancreas dysfunction are just part of the CF picture. Managing this “full-body disease” requires timely testing, traditional therapies, and familiarity with newer agents.

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References

1. Cystic Fibrosis Foundation. Patient registry 2012 annual data report. Cystic Fibrosis Foundation Web site. Available at: http://www.cff.org/UploadedFiles/research/ClinicalResearch/PatientRegistryReport/2012-CFF-Patient-Registry.pdf. Accessed August 14, 2014.

2. Haller W, Ledder O, Lewindon PJ, et al. Cystic fibrosis: An update for clinicians. Part 1: Nutrition and gastrointestinal complications. J Gastroenterol Hepatol. 2014;29:1344-1355.

3. Hoffman LR, Ramsey BW. Cystic fibrosis therapeutics: the road ahead. Chest. 2013;143:207-213.

4. Yankaskas JR, Marshall BC, Sufian B, et al. Cystic fibrosis adult care: consensus conference report. Chest. 2004;125:1S-39S.

5. Farrell PM, Rosenstein BJ, White TB, et al; Cystic Fibrosis Foundation. Guidelines for diagnosis of cystic fibrosis in newborns through older adults: Cystic Fibrosis Foundation consensus report. J Pediatr. 2008;153:S4-S14.

6. Donaldson SH, Boucher RC. Sodium channels and cystic fibrosis. Chest. 2007;132:1631-1636.

7. Flume PA, Robinson KA, O’Sullivan BP, et al; Clinical Practice Guidelines for Pulmonary Therapies Committee. Cystic fibrosis pulmonary guidelines: airway clearance therapies. Respir Care. 2009;54:522-537.

8. Flume PA, O’Sullivan BP, Robinson KA, et al; Cystic Fibrosis Foundation, Pulmonary Therapies Committee. Cystic fibrosis pulmonary guidelines: chronic medications for maintenance of lung health. Am J Respir Crit Care Med. 2007;176:957-969.

9. Döring G, Flume P, Heijerman H, et al; Consensus Study Group. Treatment of lung infection in patients with cystic fibrosis: current and future strategies. J Cyst Fibros. 2012;11:461-479.

10. Flume PA, Mogayzel PJ Jr, Robinson KA, et al; Clinical Practice Guidelines for Pulmonary Therapies Committee. Cystic fibrosis pulmonary guidelines: treatment of pulmonary exacerbations. Am J Respir Crit Care Med. 2009;180:802-808.

11. Southern KW, Barker PM. Azithromycin for cystic fibrosis. Eur Respir J. 2004;24:834-838.

12. Andersen DH. Cystic fibrosis of the pancreas and its relation to celiac disease: a clinical and pathologic study. Am J Dis Child. 1938;56:344-399.

13. Moran A, Brunzell C, Cohen RC, et al; CFRD Guidelines Committee. 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.

14. Kerem E, Conway S, Elborn S, et al; Consensus Committee. Standards of care for patients with cystic fibrosis: a European consensus. J Cyst Fibros. 2005;4:7-26.

15. Hew-Butler T, Rosner MH, Fowkes-Godek S, et al. Statement of the third international exercise-associated hyponatremia consensus development conference, Carlsbad, California, 2015. Clin J Sport Med. 2015;25:303-320.

16. Brown MB, McCarty NA, Millard-Stafford M. High-sweat Na+ in cystic fibrosis and healthy individuals does not diminish thirst during exercise in the heat. Am J Physiol Regul Integr Comp Physiol. 2011;301:R1177-R1185.

17. Wheatley CM, Wilkins BW, Snyder EM. Exercise is medicine in cystic fibrosis. Exerc Sport Sci Rev. 2011;39:155-160.

18. Ramsey BW, Davies J, McElvaney NG, et al; VX08-770-102 Study Group. ACFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med. 2011;365:1663-1672.

19. Pettit RS, Fellner C. CFTR Modulators for the Treatment of Cystic Fibrosis. P T. 2014;39:500-511.

20. Lewis D. Role of the family physician in the management of cystic fibrosis. Am Fam Physician. 2015;91:822-824.

PRACTICE RECOMMENDATIONS

› Prescribe inhaled dornase alpha and inhaled tobramycin for maintenance pulmonary treatment of moderate to severe cystic fibrosis (CF). A
› Give aggressive nutritional supplementation to maintain a patient’s body mass index and blood sugar control and to attain maximal forced expiratory volume in one second (FEV₁). B
› Consider prescribing cystic fibrosis transmembrane conductance regulator modulators, which have demonstrated a 5% to 10% improvement in FEV₁ for CF patients. A

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

Thanks to improved therapies and medical care in the last 3 decades, the treatment of cystic fibrosis (CF) is on the threshold of a new era, and the median age of survival has reached 40 years.¹ The hope of further extending survivability is now very real because of a new class of medications that act to modulate the primary pathology.

The focus of treatment. CF is not limited to the classic picture of lung and pancreas destruction with subsequent loss of function. The underlying pathology can occur in body epithelial tissues from the intestinal lining to sweat glands. These tissues contain cystic fibrosis transmembrane conductance regulator (CFTR), a protein that allows for the transport of chloride across epithelial cell membranes.² In individuals homozygous for mutated CFTR genes, chloride transport can be impaired. In addition to regulating chloride transport, CFTR is part of a larger, complex interaction of ion transport proteins such as the epithelial sodium channel (ENaC) and others that regulate bicarbonate secretion.² Decreased chloride ion transport in mutant CFTR negatively affects the ion transport complex; the result is a higher-than-normal viscosity of secreted body fluids.

Reason for hope. It is this impairment of chloride ion transport that leads to the classic phenotypic features of CF (eg, pulmonary function decline, pancreatic insufficiency, malnutrition, chronic respiratory infection), and is the target of both established and emerging therapies³—both of which I will review here.

For 90% of adults with cystic fibrosis, sweat chloride will be in the abnormal range of >60 mmol/L.

When to consider a CF diagnosis

Cystic fibrosis remains a clinical diagnosis when evidence of at least one phenotypic feature of the disease (TABLE 1) exists in the presence of laboratory evidence of a CFTR abnormality.⁴ Confirmation of CFTR dysfunction is demonstrated by an abnormality on sweat testing or identification of a CF-causing mutation in each copy of CFTR (ie, one on each chromosome).⁵ All 50 states now have neonatal laboratory screening programs;⁴ despite this, 30% of cases in 2012 were still diagnosed in those older than 1 year of age, with 3% to 5% diagnosed after age 18.¹

A sweat chloride reading in the abnormal range (>60 mmol/L) is present in 90% of patients diagnosed with CF in adulthood; this test remains the gold standard in the diagnosis of CF and the initial test of choice in suspected cases.⁴ Newborn screening programs identify those at risk by detecting persistent hypertrypsinogenemia and referring those with positive results for definitive testing with sweat chloride evaluation. Keep CF in mind when evaluating adolescents and adults who have chronic sinusitis, chronic/recurrent pulmonary infections, chronic/recurrent pancreatitis, or infertility from absence of the vas deferens.⁴ When features of the CF phenotype are present, especially if there is a known positive family history of CF or CF carrier status, order sweat chloride testing.

Traditional therapies

Both maintenance and acute therapies are directed throughout the body at decreasing fluid viscosity, clearing fluid with a high viscosity, or treating the tissue destruction that results from highly-viscous fluid.³ The traditional classic picture of CF is one of lung and pancreas destruction with subsequent loss of function. However, CF is, in reality, a full-body disease.

Respiratory system: Lungs

CFTR dysfunction in the lungs results in thick pulmonary secretions as the aqueous surface layer (ASL) lining the alveolar epithelium becomes dehydrated and creates a prime environment for the development of chronic infection. What ensues is a recurrent cycle of chronic infection, inflammation, and tissue destruction with loss of lung volume and function. Current therapies interrupt this cycle at multiple points.⁶

Airway clearance is one of the hallmarks of CF therapy, using both chemical and mechanical treatments. Daily, most patients will use either a therapy vest that administers sheering forces to the chest cavity or an airflow device that creates positive expiratory pressure and laminar flow to aid in expectorating pulmonary secretions.⁷ Because exercise has yielded comparable results to mechanical or airflow clearance devices, it is recommended that all CF patients who are not otherwise prohibited engage in regular, vigorous exercise in accordance with standard recommendations for the general public.⁷