Clinical Pearls: Cystic Fibrosis 

November 21, 2022
By Duaa Osman

This article is part of a series appearing in Interactions, our biweekly newsletter, written and researched by CSHP's students. We've created this series as a valuable learning activity for pharmacy students undertaking rotations at CSHP. Crafting these pieces not only helps students gain in-depth knowledge of specific conditions, treatments, and resources, it also helps them hone their skills in research, critical appraisal, evaluation, synthesis, and writing – all of which will serve them well in clinical practice. The Professional Practice Team works with the students to select hot topics that are of interest and utility to both the students and to you, the reader. We hope you enjoy this piece by one of our future colleagues! Let us know what you think: If you would like to provide any comments or constructive feedback for our students, please email us at practice@cshp.ca.

Background

Cystic Fibrosis (CF) is an autosomal recessive genetic disease caused by a mutation in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein resulting in abnormal ion transport across cell membranes.This altered ion transport causes CF to affect multiple organ systems such as the pulmonary, reproductive, and digestive systems.1 

Mutations to the CFTR protein can be divided into five classes which differ in severity, with classes I-III generally being more severe than classes IV-V (see Table 1). Although differences in severity may be observed based on the class of mutation, it is important for clinicians to avoid solely using these classifications to define severity.2

 

Table 1: Classification of Cystic Fibrosis CFTR mutations2,3


Patients with CF may present with shortness of breath, productive cough, digital clubbing, nasal polyps, and pancreatic insufficiency. Pulmonary function tests may also indicate a reduced forced expiratory volume at 1 second (FEV1) due to pulmonary obstruction.4

According to the Canadian Cystic Fibrosis Registry 2020 annual report, a total of 4,332 Canadians are affected by CF attributing to 1 in every 3,600 live births.5 It is estimated that the current median life expectancy of patients with CF in Canada is 55.4 years.5 Early diagnosis and treatment of CF is a crucial component of long-term survival.Current diagnostic guidelines recommend that patients presenting with any of the following undergo a sweat chloride test to screen for CF6:
  • Positive newborn screening result
  • Signs and/or symptoms of CF
  • Family history of CF (e.g., siblings diagnosed with CF)

Sweat chloride testing is regarded as the gold standard screening method for CF. Using pilocarpine ionophoresis, the test quantifies the amount of chloride present in the sweat which can be used to aid in the diagnostic process (see table 2). Due to the dysfunction of the CFTR protein, patients with CF tend to present with elevated sweat chloride concentrations.6


Table 2: Sweat chloride test result interpretation6,7

 

Management of CF: Therapeutic options 

At present, there is no available cure for CF, however several therapeutic products can be used to help manage the disease by increasing airway clearance or partially restoring CFTR function. Patients with CF may also require nutritional support such as high calorie diets, fat soluble vitamin supplementation, and pancreatic enzyme supplementation.1

Therapies aimed at increasing airway clearance help patients improve their overall lung function and reduce the risk of pulmonary infections. A combination of non-pharmacologic airway clearance techniques, such as postural drainage (conventional chest physiotherapy), active cycle breathing techniques, airway oscillating devices, and exercise8, along with pharmacologic therapies. In patients 6 years and older, the following sequence of administration is typically followed: bronchodilators, followed by mucolytics, then non-pharmacologic airway clearance techniques, then inhaled antibiotics.1,4

In addition to therapies aimed at increasing airway clearance, patients may also be treated using CFTR modulators which aim to partially restore CFTR function. Currently, 4 CFTR modulators are available in Canada, the newest of which being Trikafta® (ivacaftor/tezacaftor/elexacaftor) Trikafta® is a triple combination CFTR modulator new to the Canadian market for the treatment of CF in patients 6 years and older.9 The treatment is targeted at patients who have at least one CFTR gene mutation, specifically the F508del mutation which is estimated to affect up to 90% of patients with CF.4 Trikafta® works by binding to sites on the CFTR protein to increase its activity. When compared to baseline, patients receiving Trikafta® in clinical trials demonstrated a 14% increase in lung function. Of note, patients participating in the Trikafta® trials all continued on their existing bronchodilators, mucolytics, and inhaled antibiotics, but discontinued any other CFTR modulators.9 While CFTR modulators present many benefits to patients with CF, access to these medications remains limited due to cost barriers. First generation (Kalydeco®) and second generation (Orkambi®) modulators can be accessed through some provincial formularies; however, their access remains highly limited.

Table 3: Non exhaustive list of available therapeutic options in Canada for CF.4
 

In addition to pulmonary complications such as respiratory insufficiency, patients with CF may experience non-pulmonary complications. Examples of these complications include CF-related diabetes, pancreatic insufficiency, and osteoporosis. Due to the prevalence of complications among patients with CF, it is important that clinicians implement effective screening and preventative strategies in their care plans of patients with CF.14 

The role of pharmacists and pharmacy technicians in CF management

Due to the nature of the condition, it is integral that patients are adherent to their CF medication regimens to help prevent hospitalization and further complications. It is estimated that patients with CF are prescribed an average of 10 medications for the management of their condition. Pharmacists can play an integral role in the medication management of patients with CF to help improve adherence. A study conducted at the Intermountain Primary Children’s Hospital in the Utah found that pharmacist intervention resulted in nearly a 3-fold increase in adherence to Dornase alpha and was associated with a decrease in hospitalization rate due to non-adherence.15 In addition, the inclusion of pharmacy technicians in CF clinic specialty pharmacies resulted in reduced wait times for specialty medications through timelier deliveries. The improved efficiency of medication delivery also resulted in a decreased need for patients to utilize multiple pharmacies to access their medications.11 Overall, integrating members of the pharmacy team into the management of patients positively impacts patient care through timely access to specialty medications (through decreased delivery times and time required for prior authorization), improved patient education/adherence, and reduced hospitalization.16

 

References

1. Wright CC, Vera Y. Cystic Fibrosis. In: DiPiro JT, Yee GC, Posey L, Haines ST, Nolin TD, Ellingrod V. eds. Pharmacotherapy: A Pathophysiologic Approach, 11e. McGraw Hill; 2020. Accessed September 15, 2022. https://accesspharmacy.ca 
2. Katkin JP. Cystic Fibrosis: Genetics and pathogenesis. In: UpToDate. UpToDate; 2022. Accessed September 23, 2022. www.uptodate.com 
3. Types of CFTR mutations. Cystic Fibrosis Foundation. Accessed September 23, 2022. https://www.cff.org/research-clinical-trials/types-cftr-mutations#conduction-mutations 
4. Tang A, Crawley A. Cystic Fibrosis: Drug comparison chart. January 2022. Available from www.rxfiles.ca 
5. The Canadian Cystic Fibrosis Registry. 2020 Annual report. Published February 2022. Accessed September 21, 2022. https://www.cysticfibrosis.ca/registry/2020AnnualDataReport.pdf  
6. Farrell PM, White TB, Ren CL, et al. Diagnosis of Cystic Fibrosis: Consensus Guidelines from the Cystic Fibrosis Foundation [published correction appears in J Pediatr. 2017 May;184:243]. J Pediatr. 2017;181S:S4-S15.e1. doi:10.1016/j.jpeds.2016.09.064 
7. Katkin JP. Cystic Fibrosis: Clinical manifestations and diagnosis. In: UpToDate. UpToDate; 2022. Accessed September 20, 2022. www.uptodate.com 
8. Wilson LM, Morrison L, Robinson KA. Airway clearance techniques for cystic fibrosis: an overview of Cochrane systematic reviews. Cochrane Database Syst Rev. 2019;1(1):CD011231. Published 2019 Jan 24. doi:10.1002/14651858.CD011231.pub2
9. Vertex Pharmaceuticals. Trikafta product monograph. Available at: https://pi.vrtx.com/files/Canadapm_trikafta_en.pdf 
10. Ipratropium (Oral Inhalation). In Lexi-Drugs. Lexi-Comp, Inc. Updated October 25, 2022. Accessed November 18, 2022. https://online.lexi.com
11. Levofloxacin (Oral Inhalation). In Lexi-Drugs. Lexi-Comp, Inc. Updated November 10, 2022. Accessed November 18, 2022. https://online.lexi.com
12. Tobramycin (Oral Inhalation). In Lexi-Drugs. Lexi-Comp, Inc. Updated November 2, 2022. Accessed November 18, 2022. https://online.lexi.com
13. Aztreonam (Oral Inhalation). In Lexi-Drugs. Lexi-Comp, Inc. Updated September 19, 2022. Accessed November 18, 2022. https://online.lexi.com
14. Regard L, Martin C, Chassagnon G, Burgel PR. Acute and chronic non-pulmonary complications in adults with cystic fibrosis. Expert Rev Respir Med. 2019;13(1):23-38. doi:10.1080/17476348.2019.1552832
15. Zobell JT, Schwab E, Collingridge DS, Ball C, Nohavec R, Asfour F. Impact of pharmacy services on cystic fibrosis medication adherence. Pediatr Pulmonol. 2017;52(8):1006-1012. doi:10.1002/ppul.23743
16. Grant JJ, McDade EJ, Zobell JT, Young DC. The indispensable role of pharmacy services and medication therapy management in cystic fibrosis. Pediatr Pulmonol. 2022;57 Suppl 1:S17-S39. doi:10.1002/ppul.25613

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