Title: Cystic Fibrosis: A MultiDisciplinary Perspective on Issues Facing MUSC Patients
1Cystic Fibrosis A Multi-Disciplinary Perspective
on Issues Facing MUSC Patients
- Dr. Patrick Flume, MD
- Susan Gray, RN, MSN
- Dr. Lisa King, PharmD
- Dr. Jason Sarashinsky, PharmD
2CF is a Genetic Disease-autosomal recessive-
3Cystic Fibrosis Foundation Consensus Statement
- Diagnosis of CF
- One or more characteristic phenotypic features,
or - A history of CF in a sibling, or
- A positive newborn screening test, plus
- Evidence of a CFTR abnormality
4The Sweat Gland
5Sweat Test for Cystic Fibrosis
6Complications of Cystic Fibrosis
- Pulmonary
- chronic airways infection
- bronchiectasis
- Sinuses
- chronic sinusitis
- Pancreatic
- enzyme deficiency
- malabsorption
- diabetes mellitus
- Gastrointestinal
- GERD
- bowel obstruction (DIOS)
- Hepatobiliary
- biliary cirrhosis
- cholelithiasis
- Genito-urinary
- infertility (CBAVD)
7Pathogenesis of CF Lung Disease
CF Gene Mutations
CFTR Dysfunction
Ion Transport Abnormalities
Altered Airway Secretions
Vicious cycle
Infection
Inflammation
Tissue Damage
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11Incidence of Major Airway Pathogens by Patient Age
FitzSimmons J Pediatr 122 1-9 1993
12The Vicious Cycle Obstruction, Infection, and
Inflammation
13Progression of CF Airways Disease
100
After treatment
80
60
FEV1 ( predicted)
40
Exacerbations
20
0
Age (y)
- Acute exacerbations with some reversibility
- Chronic decline
14What is an exacerbation?
- Increased cough
- Increased sputum
- Change in sputum (more purulent, hemoptysis)
- Decline in lung function (spirometry)
- New infiltrate on CXR
- Fever, chest pain
- Decreased appetite
- Loss of weight
15Progression of CF Airways Disease
100
After treatment
80
60
FEV1 ( predicted)
40
Exacerbations
20
0
Age (y)
- Acute exacerbations with some reversibility
- Chronic decline
16Theoretical CF Survival Curves
1.0
P aeruginosa Negative
0.75
Proportion Surviving
0.5
P aeruginosa Positive
0.25
0
0
5
10
15
20
25
30
35
Age (y)
Data compiled from Cystic Fibrosis Foundation
Patient Registry, 19961999.
17Median Age of Survival in CF
18Why has Survival Improved?
- Nutrition
- Antibiotics
- Airway clearance techniques
- Center care
- Improved diagnostic measures
- Transplantation
19CF Center Accreditation
- Specific personnel
- Regular team meetings
- Hospital for inpatient care
- Clinic area
- ½-day clinic each week
- Laboratory function
- Sweat test, micro, chemistries, CXR
- RT available 24/7
- 50 pt minimum
- Adult program
- Age appropriate care
- Submission of annual report, Registry Data,
Periodic Status Report - Consultation available
- Referral plan
- transplant
20Cystic Fibrosis Foundation
MUSC Cystic Fibrosis Center
Pediatric CF Program
Adult CF Program
Components of a CF Center Clinical
care Teaching Research
21The MUSC Experience
- 1958 Crippled Childrens Hospital Svc.
- 1978 Multidisciplinary Team approach
- 1993 Adult CF Center established
- 2004 Quality Improvement focus
22The CF Team
23MUSC Center Statistics
24MUSC CF Patients
25New Diagnoses of CF (US)
Year 2001 2002 2003
New Dx 1,013 972 958
- Total number 21,742
- CFF Patient Registry, 2003
26American College of Obstetricians and
Gynecologists
ACOG now recommends that ob-gyns make DNA
screening for cystic fibrosis available to all
couples seeking preconception or prenatal care
not just those with a personal or family history
of carrying the CF gene, as previously
recommended.
27Newborn Screening in SC
Phenylketonuria (PKU) Congenital
hypothyroidism Galactosemia Hemoglobinopathy
Disorders and Traits Congenital adrenal
hyperplasia Medium chain acyl-CoA dehydrogenase
deficiency
and nowcystic fibrosis
28Transition
Adult
Adolescent
29MUSC Method of Transition
- New patient phase
- all new patients meet adult team as early as
possible - Reinforcement phase
- adult team meets with teen at age 14
- parents are out of the room for part of
subsequent clinic visits - The Transfer
- all care is transferred to adult team
- summer following 18th birthday
30Criteria for Successful Transition
- Commitment
- Preparation
- Timing
- Coordination
31Pulmonary and Nutritional Management
- Overall goals of therapy
- Mobilize secretions
- Control the infection-inflammation cycle
- Improve nutritional status of patient to improve
growth
32Progression of CF Airways Disease
100
After treatment
80
60
FEV1 ( predicted)
40
Exacerbations
20
0
Age (y)
- Acute exacerbations with some reversibility
- Chronic decline
33Chronic Management
- Respiratory Therapy
- Anti-inflammatory measures
- Nutrition
- Diabetes
34Respiratory Therapy
- Airway clearance techniques
- Beta-agonists
- Albuterol MDI or hand held nebulizer
- Mucolytics
- rhDNase (Pulmozyme)
- Reduces viscosity of sputum
- May lower incidence of pulmonary exacerbations
35Anti-Inflammatory Therapy
- Chronic bacterial infection is stimuli for
inflammation - Goal of therapy
- Decrease rate of decline in pulmonary function
- Oral corticosteroids
- Inhaled corticosteroids
- Ibuprofen
- Macrolides (Azithromycin)
36Antimicrobial Theories
- Bacterial colonization vs. pathogen
- Do we treat all infections?
- Non-bacterial causes of exacerbation
- Allergens, viral infections, air pollutants
- Antibiotics are used to improve or delay decline
in pulmonary function
37Antimicrobial Theories
- Indications for Antibiotic Use
- Prevent colonization of chronic P. aeruginosa
bacteria - Maintenance therapy slows decline in pulmonary
function - Intense regimens relieve symptoms and restore
baseline pulmonary function
38First Query
- What are the most common bacterial pathogens
isolated from respiratory secretions in an adult
patient? - Staphylococcus aureus
- Haemophilus influenzae
- Pseudomonas aeruginosa
- Others
- Burkholderia cepacia
- Stenotrophomonas maltophilia
39Chronic Suppressive Antibiotic Therapy
- Inhaled Antibiotics
- Improves drug delivery and decreases systemic
toxicity while improving overall lung function - Tobi
- Significant, sustained improvement in pulmonary
function - Colistin
- Different mechanism of action, but efficacy is
still being studied - Gentamicin (seen in pediatrics)
40Long-term Intermittent Inhaled Tobramycin in
Cystic Fibrosis
On Drug
On Drug
On Drug
16
14
12
10
TSI(n 2571)
8
6
Mean Relative Change in FEV1 Predicted
11.9 p 4
2
0
Placebo (n 2621)
-2
-4
-6
0
2
4
6
8
12
16
20
24
Week
Ramsey BW, et al. N Engl J Med. 19993402330.
41Antibiotic Use in CF Disease
- Outpatient versus Inpatient
- Appropriate if exacerbation is mild and pathogens
are sensitive - S. aureus treated with cephalosporins
- P. aeruginosa treated with fluoroquinolones
42Antibiotic Use in CF Disease
- IV antibiotics (Inpatient Management)
- Initial selection is empiric for pathogen and
patient age - Treatment of P. aeruginosa
- Aminoglycoside Beta-lactam antibiotic
- Higher doses to compensate for kinetic changes
(Increased Vd, altered renal clearance)
43Antibiotic Therapy
- Beta-Lactams
- Aminoglycosides
- Tobramycin first line
- Quinolones
- Ciprofloxacin first line
- Meropenem
- Ticarcillin
- TMP-SMX
- Vancomycin (MRSA colonization)
44Nutrition
- Essential part of treatment plan
- Monitor growth (height and wt)
- CF patients have increased caloric needs
- 30-50 greater requirements
- Increased energy expenditure
- Decreased appetite
45Nutritional Goals
- Increased caloric intake
- Increase food intake (no restrictions)
- Dietary supplements (Boost, Ensure)
- Tube feedings overnight
- Parenteral nutrition for short term use
- Reduce Malabsorption
- Enzyme supplementation
- Vitamin supplementation
- Multivitamins
- ADEK
46Pancreatic System
- Primary source of digestive enzymes and insulin
production - Blockage of exocrine outflow prevents enzyme
release- pancreas slowly digests itself - Malabsorption of fats, proteins, carbohydrates,
fat soluble vitamins - Complications
- Numerous foul smelling stools
- Altered appetite and growth retardation
- Abdominal distension
- Diabetes Mellitus
47Pancreatic Enzyme Supplements
- 90 of patients need supplementation
- Contain lipase, amylase, protease
- Individualized doses
- Titrate based on signs of fat malabsorption
- Frequency of stools, steatorrhea, abdominal
cramping, degree of fullness - Excess amounts of enzyme leads to constipation
48Pancreatic Enzyme Supplements
- Microencapsulated microspheres
- pH sensitive, protect from gastric acid
degradation - Infants/ Children
- Open capsules and sprinkle beads on applesauce,
rice cereal or baby food - Feeding tubes
- Pt may take by mouth before tube feeds started
- Do not substitute products
- No generic substitutions
49Cystic Fibrosis Related Diabetes (CFRD)
- Major complication with older CF patients
- Exocrine obstruction prevents insulin secretion
- Patients develop more insulin receptor sites, but
with decreased affinity for insulin - 15-40 of pt 35 y/o require insulin
- Associated with increased morbidity and mortality
50Diabetic Glucose Control
- Treat aggressively with insulin
- Nutritional management
- Close attention to timing of meals
- Fasting hyperglycemia and ketosis uncommon
- Basal insulin secretion still functional
- Short acting insulin (ie. Novolog) prior to meals
- Monitoring
- Home glucose testing
- Hemoglogin A1c
51Complications of Cystic Fibrosis
- Pulmonary
- chronic airways infection
- bronchiectasis
- Sinuses
- chronic sinusitis
- Pancreatic
- enzyme deficiency
- malabsorption
- diabetes mellitus
- Gastrointestinal
- GERD
- bowel obstruction (DIOS)
- Hepatobiliary
- biliary cirrhosis
- cholelithiasis
- Genito-urinary
- infertility (CBAVD)
52Treatment of CF Airways Disease
- Remove secretions/reduce obstruction
- Reduce inflammation
- Treat infection
- Address other complicating features
- nutrition
- diabetes mellitus
- GERD
- sinusitis
53Medication and Therapy Counter 0
54Lung Bronchodilator (Albuterol)
Medication and Therapy Counter 1
55Lung Bronchodilator (Albuterol) Pulmozyme
Medication and Therapy Counter 2
56Lung Bronchodilator (Albuterol) Pulmozyme
TOBI
Medication and Therapy Counter 3
57Lung Bronchodilator (Albuterol) Pulmozyme
TOBI Hypertonic saline
Medication and Therapy Counter 4
58Lung Bronchodilator (Albuterol) Pulmozyme
TOBI Hypertonic saline Airway clearance
techniques
Medication and Therapy Counter 5
59Lung Bronchodilator (Albuterol) Pulmozyme
TOBI Hypertonic saline Airway clearance
techniques Sinuses Nasal steroids (Flonase)
Medication and Therapy Counter 6
60Lung Bronchodilator (Albuterol) Pulmozyme
TOBI Hypertonic saline Airway clearance
techniques Sinuses Nasal steroids (Flonase)
Nasal irrigation
Medication and Therapy Counter 7
61Lung Bronchodilator (Albuterol) Pulmozyme
TOBI Hypertonic saline Airway clearance
techniques Sinuses Nasal steroids (Flonase)
Nasal irrigation Pancreas Digestive enzymes
Medication and Therapy Counter 8
62Lung Bronchodilator (Albuterol) Pulmozyme
TOBI Hypertonic saline Airway clearance
techniques Sinuses Nasal steroids (Flonase)
Nasal irrigation Pancreas Digestive enzymes
Multivitamins
Medication and Therapy Counter 9
63Lung Bronchodilator (Albuterol) Pulmozyme
TOBI Hypertonic saline Airway clearance
techniques Sinuses Nasal steroids (Flonase)
Nasal irrigation Pancreas Digestive enzymes
Multivitamins Insulin
Medication and Therapy Counter 10
64Lung Bronchodilator (Albuterol) Pulmozyme
TOBI Hypertonic saline Airway clearance
techniques Sinuses Nasal steroids (Flonase)
Nasal irrigation Pancreas Digestive enzymes
Multivitamins Insulin Glucose checks
Medication and Therapy Counter 11
65Lung Bronchodilator (Albuterol) Pulmozyme
TOBI Hypertonic saline Airway clearance
techniques Sinuses Nasal steroids (Flonase)
Nasal irrigation Pancreas Digestive enzymes
Multivitamins Insulin Glucose checks Etc.
Ibuprofen
Medication and Therapy Counter 12
66Lung Bronchodilator (Albuterol) Pulmozyme
TOBI Hypertonic saline Airway clearance
techniques Sinuses Nasal steroids (Flonase)
Nasal irrigation Pancreas Digestive enzymes
Multivitamins Insulin Glucose checks Etc.
Ibuprofen Ursodeoxycholic acid
Medication and Therapy Counter 13
67Lung Bronchodilator (Albuterol) Pulmozyme
TOBI Hypertonic saline Airway clearance
techniques Sinuses Nasal steroids (Flonase)
Nasal irrigation Pancreas Digestive enzymes
Multivitamins Insulin Glucose checks Etc.
Ibuprofen Ursodeoxycholic acid Acid
suppression (Prevacid/Zantac)
Medication and Therapy Counter 14
68Lung Bronchodilator (Albuterol) Pulmozyme
TOBI Hypertonic saline Airway clearance
techniques Sinuses Nasal steroids (Flonase)
Nasal irrigation Pancreas Digestive enzymes
Multivitamins Insulin Glucose checks Etc.
Ibuprofen Ursodeoxycholic acid Acid
suppression (Prevacid/Zantac)
AM X
noon
PM
bedtime
TIME 10 min
PILLS
69Lung Bronchodilator (Albuterol) Pulmozyme
TOBI Hypertonic saline Airway clearance
techniques Sinuses Nasal steroids (Flonase)
Nasal irrigation Pancreas Digestive enzymes
Multivitamins Insulin Glucose checks Etc.
Ibuprofen Ursodeoxycholic acid Acid
suppression (Prevacid/Zantac)
AM X X
noon
PM
bedtime
TIME 20 min
PILLS
70Lung Bronchodilator (Albuterol) Pulmozyme
TOBI Hypertonic saline Airway clearance
techniques Sinuses Nasal steroids (Flonase)
Nasal irrigation Pancreas Digestive enzymes
Multivitamins Insulin Glucose checks Etc.
Ibuprofen Ursodeoxycholic acid Acid
suppression (Prevacid/Zantac)
AM X X X
noon
PM
bedtime
TIME 40 min
PILLS
71Lung Bronchodilator (Albuterol) Pulmozyme
TOBI Hypertonic saline Airway clearance
techniques Sinuses Nasal steroids (Flonase)
Nasal irrigation Pancreas Digestive enzymes
Multivitamins Insulin Glucose checks Etc.
Ibuprofen Ursodeoxycholic acid Acid
suppression (Prevacid/Zantac)
AM X X X X
noon
PM
bedtime
TIME 1 hr 10 min
PILLS
72Lung Bronchodilator (Albuterol) Pulmozyme
TOBI Hypertonic saline Airway clearance
techniques Sinuses Nasal steroids (Flonase)
Nasal irrigation Pancreas Digestive enzymes
Multivitamins Insulin Glucose checks Etc.
Ibuprofen Ursodeoxycholic acid Acid
suppression (Prevacid/Zantac)
AM X X X X X
noon
PM
bedtime
TIME 1 hr 20 min
PILLS
73Lung Bronchodilator (Albuterol) Pulmozyme
TOBI Hypertonic saline Airway clearance
techniques Sinuses Nasal steroids (Flonase)
Nasal irrigation Pancreas Digestive enzymes
Multivitamins Insulin Glucose checks Etc.
Ibuprofen Ursodeoxycholic acid Acid
suppression (Prevacid/Zantac)
AM X X X X X X
noon
PM
bedtime
TIME 1 hr 20 min
PILLS
74Lung Bronchodilator (Albuterol) Pulmozyme
TOBI Hypertonic saline Airway clearance
techniques Sinuses Nasal steroids (Flonase)
Nasal irrigation Pancreas Digestive enzymes
Multivitamins Insulin Glucose checks Etc.
Ibuprofen Ursodeoxycholic acid Acid
suppression (Prevacid/Zantac)
AM X X X X X X X
noon
PM
bedtime
TIME 1 hr 20 min
PILLS 4
75Lung Bronchodilator (Albuterol) Pulmozyme
TOBI Hypertonic saline Airway clearance
techniques Sinuses Nasal steroids (Flonase)
Nasal irrigation Pancreas Digestive enzymes
Multivitamins Insulin Glucose checks Etc.
Ibuprofen Ursodeoxycholic acid Acid
suppression (Prevacid/Zantac)
AM X X X X X X X X
noon
PM
bedtime
TIME 1 hr 20 min
PILLS 5
76Lung Bronchodilator (Albuterol) Pulmozyme
TOBI Hypertonic saline Airway clearance
techniques Sinuses Nasal steroids (Flonase)
Nasal irrigation Pancreas Digestive enzymes
Multivitamins Insulin Glucose checks Etc.
Ibuprofen Ursodeoxycholic acid Acid
suppression (Prevacid/Zantac)
AM X X X X X X X X X X
noon
PM
bedtime
TIME 1 hr 30 min
PILLS 5
77Lung Bronchodilator (Albuterol) Pulmozyme
TOBI Hypertonic saline Airway clearance
techniques Sinuses Nasal steroids (Flonase)
Nasal irrigation Pancreas Digestive enzymes
Multivitamins Insulin Glucose checks Etc.
Ibuprofen Ursodeoxycholic acid Acid
suppression (Prevacid/Zantac)
AM X X X X X X X X X X
noon X X X X
PM X X X X X X
bedtime X X X X X X X X X
TIME 4 hr
PILLS 14
78Lung Bronchodilator (Albuterol) Pulmozyme
TOBI Hypertonic saline Airway clearance
techniques Sinuses Nasal steroids (Flonase)
Nasal irrigation Pancreas Digestive enzymes
Multivitamins Insulin Glucose checks Etc.
Ibuprofen Ursodeoxycholic acid Acid
suppression (Prevacid/Zantac)
AM X X X X X X X X X X X X X
noon X X X X
PM X X X X X X X X
bedtime X X X X X X X X X X X X
TIME 4 hr
PILLS 25