Cystic Fibrosis - Extended version

Objectives:

1. Develop an understanding of the molecular pathogenesis and CFTR dysfunction along with the natural history of the disease
2. Appreciate the myriad of organ system involvement (upper/lower respiratory tract, GI/nutrition, endocrine, reproductive, electrolyte complications, etc.)
3. Recognize infectious complications of CF lung disease (e.g. Pseudomonas aeruginosa, MRSA, Burkholderia cepacia ABPA, nontuberculous mycobacterial infection)
4. Understand the inpatient presentation and the treatment of pulmonary exacerbations and the complications of CF involving other organ systems
5. Appreciate the importance of a multidisciplinary team approach
6. Understand diagnostic testing, including sweat testing, genetic testing and newborn screening
7. Know the basis of CF maintenance therapy and care in an outpatient setting
8. Review the use of CFTR modulator therapies
9. Recognize the importance of therapy adherence and barriers to care

Articles:

• There have been great advances in CF management over the past few decades. Read this 2020 review article from the Lancet Respiratory Medicine Commission to appreciate how CF care has evolved over time and better understand the natural history of the disease through a patient’s lifetime.  In addition, the paper offers a unique global perspective on CF.  [Objectives 1-9]
• For a better understanding of the multiple organ systems impacted by CF, please see the following Pediatrics in Review review article on lung, gastrointestinal and pancreatic complications. [Objectives 1-4, 6, 7]
• This state-of-the-art review article discusses the most common lung infections affecting cystic fibrosis patients.  It provides a great review of the pathophysiology, presentation, diagnosis and treatment of these infections.  There is a great explanation of how CFTR dysfunction predisposes patients to colonization by Pseudomonas aeruginosa. [Objective 1-4, 7]
• These guidelines on the management of acute pulmonary exacerbations highlight the recommendedantibiotic regimens, including the dosing and duration antibiotic treatment with graded evidence.  For more information on the treatment of lung infections with a focus on Pseudomonas aeruginosa read this review article. [Objective 2-4]
• CF requires multidisciplinary care that must be standardized across institutions. The Cystic fibrosis Care Center Network exemplifies the importance of a team-based approach to improve patient outcomes as evidenced by this 2013 BMJ article. [Objective 5]
• CF is caused by dysfunction of the cystic fibrosis transmembrane receptor (CFTR). For a better understanding of the classes of CFTR mutations, their impacts on different organ systems and potential treatment targets, please see these review articles from the Lancet Respiratory Medicine and the NEJM.  For an even more in-depth understanding, check out this article on the pathophysiology of cystic fibrosis. [Objectives 1-3, 6-9]
• CF also impacts the reproductive health of both men and women! [Objective 2]
• There have been an increasing number of CF patients living into adulthood as a result of advances in treatment. However, this population faces many age-related complications involving a myriad of organ systems including the lungs, pancreas, vascular system, kidneys, bones, liver and intestines. [Objective 2]
• Allergic bronchopulmonary aspergillosis (ABPA) can be challenging to diagnose in patients with CF.  To better understand the pathogenesis, presentation, diagnosis and treatment of this disorder please review this 2017 review article. [Objective 3]
• Here are guidelines on the diagnosis and treatment of non-tuberculous mycobacterial infection in pediatric cystic fibrosis patients. [Objective 3]
• Newborn screening for cystic fibrosis is universal across the United States to capture infants at risk for the disease. It is very important to understand screening and the appropriate steps to confirm the disease. This review article provides critical information on the cystic fibrosis newborn screen as well as subsequent steps including sweat and genetic testing.  This paper also addreses the best way to communicate this information to patients and their families. [Objective 6]
• This is a clinical flow chart on the diagnosis of cystic fibrosis. It offers an easy way to interpret sweat chloride results and determine appropriate future testing. [Objective 6]
• The Cystic Fibrosis Foundation (CFF) has in-depth guidelines on the diagnosis of CF. This document provides an excellent understanding of how to interpret cystic fibrosis sweat testing and when to pursue genetic testing. [Objective 6]
• Clinical care schedules are critical for CF patients from newborn to age 5.  This table format is very quick and easy to read for knowing the necessary care at scheduled well-child visits. [Objective 7]
• These are guidelines on caring for newly diagnosed asymptomatic infants with cystic fibrosis. [Objective 2-4, 7]
• These are updated 2012 CFF guidelines on recommended maintenance therapies for cystic fibrosis patients. [Objectives 3, 7]
• Guidelines from the International Society for Pediatrics and Adolescent Diabetes on the screening, treatment and complications of cystic fibrosis-related diabetes.[Objective 2, 7]
• For a great review of CF endocrine complications and management guidelines, please reference this grand rounds on ‘Managing the Endocrine Complications of Cystic Fibrosis: A UMass Subspecialty Collaboration’ presented by our very own Dr. Darukhanavala. [Objectives 2, 7]
• This paper is a review of the pathophysiology, presentation, diagnosis and treatment of CF bone disease. Figure 2 in this paper provides a wonderful flowchart on the treatment of bone disease based on screening results. [Objectives 2, 7]
• Cystic Fibrosis Foundation guidelines for nutrition and gastrointestinal diseases, including colorectal cancer screening, enteral tube feeding, nutrition, pancreatic enzyme replacement and vitamin D deficiency. [Objective 2, 7]
• Great review article on the pathophysiology of gastrointestinal disease including pancreatic, intestinal, and hepatobiliary complications of cystic fibrosis. [Objective 1, 2, 4]
• Multidisciplinary teams are essential to provide optimal care to CF patients.  For guidelines on implementing multidisciplinary team-based care, please see this European article. [Objective 5]
• Cystic fibrosis modulator therapies remain an active area of research to improve the course of the disease. These guidelines provide a review of the currently available CFTR modulator therapies. [Objective 8]
• CFTR modulators impact multiple organs in addition the lungs. For a review of the extra pulmonary benefits, please see this review article. [Objective 2, 8]
• This 2019 review article provides a great review of clinical trial data and efficacy of cystic fibrosis modulator therapies.[Objective 8]
• Elexacaftor-tezacaftor-ivacaftor triple therapy has been shown to be more efficacious than dual therapy for patients over the age of 12 with at least one copy of the F508del variant. [Objective 8]
• For a great review of the current literature and landmark studies, please reference this pulmonology grand rounds presentation from Dr. Kremer and Dr. Dy on CFTR and a Path to a Cure. [Objectives 1, 2, 8]
• Transitioning from pediatric to adult care can pose many challenges for CF patients! These review articles from Pediatrics and Pediatric Pulmonology highlight the barriers and solutions to optimize the transition of care. [Objective 9]
• Cystic fibrosis patients face many barriers to treatment adherence which negatively impacts the severity of their disease. This pilot study by the Partnerships for Sustaining Daily Care Program looks at the patient-caregiver interaction to identify barriers and solution to adherence. [Objective 9]
• This CFF handout addresses the high cost and available coverage of CF treatments. [Objective 9]

Additional resources:

• For more guidelines on the care of cystic fibrosis patients, visit the website of the Cystic Fibrosis Foundation.
• Cystic Fibrosis My Way is an excellent video series from CHOP highlighting the proper use of cystic fibrosis therapies for patients and their families.
• Fantastic book for patients and their families on living with cystic fibrosis.
• Easy to read guide on the diagnosis and management of cystic fibrosis related diabetes. Provides great information for families on nutrition and counting carbohydrates.
• Wonderful resources for children from Johns Hopkins including coloring pages and games related to cystic fibrosis.
• The cystic fibrosis foundation provides resources for families to better understand airway clearance.