Cystic Fibrosis Overview - General Concepts

Autosomal recessive; The white race (90%)

Cystic Fibrosis is an _____ disorder, and is mostly seen in _______

• lower lung function = higher death rate

• Delayed diagnosis

• Rare mutations

• Lower representation in clinical trials

Some disparities seen in Cystic fibrosis are

CFTR protein; The variant on chromosome 7

Cystic fibrosis results in a mutation in _____ , and the function of the protein depends on 

1. No functional CFTR created

2. CFTR created, but is misfolded and does not reach protein surface to release chloride 

3. CFTR protein created and reaches surface of cell, but does not let chloride through (gate dysfunction)

4. Faulty CTFR gate opening (releases some chloride, but not much)

5. Insufficient CFTR quantities 

The different classifications of CFTR mutations

Salt in sweat (decreased chloride release)

For a defective CFTR, you may see more _______

It is located through the body, and results in thick and viscous mucosal secretions, which can cause

• Bronchiectasis in lungs (lung damage)

• Pancreatic insufficiency (mucus+secretion blocks pancreas ducts over time)

Why is CFTR important?

• Bile ducts - cause liver disease

• Bone - cause osteoporosis

• Upper airways - chronic sinusitis

• Pancreas - cause diabetes from pancreatic insufficiency

Other organ systems that are affected by CFTR gene + mucus secretions

• carrier screening, chorionic villus sampling, amniocentesis

How do clinicians screen for Cystic fibrosis in preconception/pregnancy/prenatal?

• Immunoreactive trypsinogen (IRT)

• DNA testing for mutations

How do clinicians screen for cystic fibrosis in newborns (NBS)? 

1. NBS screening or clinically suspected CF (like meconium ileus as infant)

2. Sweat chloride testing (GOLD STANDARD)

How to Diagnose Cystic Fibrosis

> 60 mEq/L

A chloride level of ______ is diagnostic for CF

Inflammation leads to infection, which leads to obstruction, which causes

• Increased energy expenditure

• Bronchiectasis

Pulmonary system cycle of CF inflammation/nfection/obstruction

Obstruction (like from pancreatic insufficiency - 85% of CF patients) - causes no digestive enzymes, which causes malabsorption

• causes failure to thrive and worsening lung disease

Digestive system cycle of CF

1. Preserve Lung Function

2. Maintain Adequate Nutrition

3. Optimize Quality Of Life

Three GENERAL goals of therapy for treating Cystic Fibrosis

• PFTs (for patients older than 5)

• Exacerbations

• Symptoms

• Radiography

• Bronchoscopy prn

How do we assess lung function in CF?

• Growth parameters (WFL/BMI percentiles)

• GI symptoms

How do we assess GI function in CF?

1. Maintain FEV1

2. Reduce number of APE (acute exacerbations)

3. Control respiratory symptoms

Lung specific goals for Cystic Fibrosis treatment

• Maintain nutrition and keep BMI/WFL percentile > 50 (weight for length/BMI) 

GI specific goals of therapy in cystic fibrosis

• Maintain normal growth + development

• WFL > 50th percentile by 2 years

• Delay the onset of pulmonary disease and pulmonary infections

Infant Goals of therapy in cystic fibrosis

Symptomatic (supportive) therapy - treats symptoms and also:

• Slows disease

• improve QOL

• lung and GI focused

The most effective therapy for CF at the moment is still _____

Mutation-specific therapy

CFTR modulator therapy is ______ and not available for all mutation types

Last line treatment!

Lung transplantation in CF management is _____

recommended

Pharmacists are part of the _______ care team for RF, not the required

Medications, counseling, collaboration, quality improvement 

Role of pharmacists in CF treatment

Pulmonary Deterioration

_____ is the primary contribution to CF mortality and morbidity (Death)