Living and Breathing with CF: Adult CF Care

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Living and Breathing with CF Adult CF Care

• Dixie Durham, MHS, CRC, RRT-NPS
• CF Center of Idaho
• Boise, ID

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Introduction

• One of the most common fatal genetic disorders in
  the US
• Classic diagnostic triad elevated sweat Cl-,
  pancreatic insufficiency, and chronic pulmonary
  disease (as always in medicine, its not this
  simple!)
• Cause defect in a single gene on chromosome 7
  that encodes a chloride channel called the cystic
  fibrosis transmembrane regulator (CFTR)
• Classically considered a childhood disease, but
  this is no longer true.

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Common CF Symptoms

• People with CF can have a variety of symptoms,
  including
• very salty-tasting skin
• persistent coughing, at times with phlegm
• frequent lung infections
• wheezing or shortness of breath
• poor growth/weight gain in spite of a good
  appetite and
• frequent greasy, bulky stools or difficulty in
  bowel movements.

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Sweat Chloride Level Is Inversely Related to CFTR
Protein Function
CBAVDcongenital bilateral absence of the vas
deferens PIpancreatic insufficiency
PSpancreatic sufficiency.Adapted from Rowe SM,
et al. Proc Am Thorac Soc. 20074(4)387-398.
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Relationship Between CFTR ProteinActivity and
Clinical Manifestations

• CF is the most severe condition of a spectrum of
  diseases associated with impaired CFTR protein
  function
• The severity of the clinical manifestations is
  linked to the degree of this impairment

ABPAallergic bronchopulmonary aspergillosis.Adap
ted from Strausbaugh SD, Davis PB. Clin Chest
Med. 200728(2)279-288.
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Median Predicted Survival Age, 1985-2006 (with 95
percent confidence bounds)
42
40
38
36
34
Median Survival Age (Years)
32
30
28
26
24
'85
'86
'87
'88
'89
'90
'91
'92
'93
'94
'95
'96
'97
'98
'99
'00
'01
'02
'03
'04
'05
'06
Year
The median predicted survival is 36.9 years for
2006. This represents the age by which half of
the current CF Registry population would be
expected to be dead, given the ages of the CF
patients in the Registry and the mortality
distribution of the deaths in 2006. The whiskers
represent the 95 percent confidence bounds for
the survival estimates, so the 2006 median
predicted survival is between 34.4 and 41.4
years.
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Survival by Birth Cohort
100
2000-2004
98
1995-1999
96
1990-1994
94
92
1985-1989
Percent Surviving
90
88
86
84
1980-1984
82
80
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
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Age (Years)
Actual survival of CF patients in the Registry
has steadily improved since 1980. Of patients
born between 1980 and 1984 (the earliest cohort
shown here), 90.2 percent survived to age 15.
For patients born between 1990 and 1994, 95.2
survived to age 15.
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Age Distribution of the CF Patient Population,
2006
1,000
100
800
80
600
60
Cumulative Percent
Number of CF Patients
400
40
200
20
0
0
0
10
20
30
40
50
60
70
Age (Years)
Number of CF Patients
Cumulative Percent
The median age is 16.2 years. 45 of patients
are gt 18 y.o.
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CF Statistics

• About 1,000 new cases of cystic fibrosis are
  diagnosed each year.
• Newborn screening in most states.
• More than 70 of patients are diagnosed by age
  two. If not caught by newborn screening, the
  average age at diagnosis is 14 months.
• In the CF Center of Idaho, 50 of our
  population is 18 or older

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Genetics and Epidemiology

• CF is autosomal recessive
• Incidence of CF
• Caucasians 1 in 2,500 (1 in 29 are carriers)
• Latinos 1 in 9,000 (1 in 46 are carriers)
• African Americans 1 in 15,000 17,000 (1 in 65
  are carriers)
• Asians 1 in 32,000 90,000 (1 in 90 are
  carriers)
• More than 1500 different mutations of the CF gene
  have been identified numerous other
  polymorphisms have also been identified
• Most common is delta-F508 deletion of
  phenylalanine at position 508 of this protein.
  This accounts for 70 of alleles in the U.S.
• Different alleles convey different severities of
  illness
• Modifier genes affect severity of illness among
  identical genotypes

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Year1-3
1. Adapted from Patient Registry 2006 Annual
Report. Bethesda, MD Cystic Fibrosis Foundation
2006. 2. Cystic Fibrosis Foundation Web site.
http//www.cff.org/aboutCFFoundation/PressRoom/200
8PressReleases/index.cfm?ID8749TYPE3617.
Accessed September 26, 2008.
3. Davis PB. Am J Respir Crit Care Med.
2006173(5)475-482. 4. Cystic Fibrosis
Foundation Web site.
http//www.cff.org/research/Research
Milestones/. Accessed July 11, 2008. 4. Dalemans
W, et al. Nature. 1991354(6354)526-528.

5. Amaral MD, Kunzelmann K. Trends
Pharmacol Sci. 200728(7)334-341.
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CF Upper Respiratory Disease

• Chronic pansinusitis
• Radiographic changes are constantly present
• Only treat with antibiotics if symptomatic
• Same microbiology as the lunguse the same
  antibiotics
• Nasal polyposis
• Allergic rhinitis

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Pancreatic Disease

• Pancreatic insufficiency
• Patients who are initially pancreatic sufficient
  often gradually become insufficient over time
• Pancreatitis
• occurs much more commonly in pancreatic
  sufficient patients than in insufficient patients
• CF related diabetes mellitus
• Often brought on by acute illness, pregnancy,
  steroid use, other physiologic stresses

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Pancreas
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Pancreatic/Intestinal Disease

• Malabsorption of nutrients is the primary problem
  for CF patients of all ages
• Must eat more calories (150 of recommended for
  age group)
• Must eat more fat (40 grams plus, depending on
  age)
• Must take replacement pancreatic enzymes
• Many problems absorbing vitamins and minerals
• Must eat more salt than the rest of us,
  especially in summer
• Failure to secrete chloride, and therefore water
  into the lumen, results in severely thickened and
  sometimes inspissated fecal contents this can
  sometimes be counterbalanced by the steatorrhea
  from pancreatic insufficiency.
• Too much pancreatic enzyme can lead to distal
  intestinal obstruction syndrome (no more than
  10,000 units of lipase per kilogram per day to be
  take)
• Supplement vitamins A, D, E, and K (ADEK or
  Vitamax)

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CF Related Diabetes

• Cant be treated as Type I or Type II diabetes
• Often brought on by acute illness, pregnancy,
  steroid use, other physiologic stresses
• Can NOT, under any circumstances, limit calories,
  fat intake, or protein intake
• Can not restrict salt
• Must frequency adjust meal plan due to pulmonary
  exacerbations

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Adult Nutritional Goal

• Goal is a BMI of 22-23
• Less than 19 considered undernourished
• More than 23 is considered fine
• Keeping a healthy body weight means better able
  to fight off infections

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CF Hepatobiliary Disease

• Gall bladder disease (cholelithiasis,
  cholecystitis, microgallbladder) is common
• Progressive liver disease can occur
• Cirrhosis in 1 3
• Hepatobiliary disease responsible for death in
  about 5 of the CF population

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CF Sexual Disease

• Congenital bilateral absence of the vas deferens
  (CBAVD)
• Almost universal in CF (95 of males with CF are
  infertile)
• Results in azoospermia, and male infertility
• Female relative infertility
• Mainly due to thickened cervical and endometrial
  secretions, impairing fertilization and
  implantation

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CF Joint and Bone Disease

• CF Reactive Arthritis
• Must be differentiated from other causes of
  arthritisJRA, SLE, infectious, etc.
• Can present very impressively, with pain,
  swelling, warmth, erythema, purpura, etc.
• Treatment
• High dose NSAIDsibuprofen vs. naproxen
• Steroid burst vs. taper if necessary (usually
  symptoms melt away rapidly)
• Osteopenia, osteoporosis, pathologic fractures
• Mostly an issue of adults
• Guidelines for evaluation and care still being
  developed

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Pain

• In one study, 95 of the adults reported having
  pain in at least one area
• Headaches reported most frequently
• Stomach or abdominal pain second most frequently
  reported
• Joint pain a frequent issue

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Other challenges

• Infection control
• Sterilizing equipment
• Hospitalizations
• Staying healthy
• Fitting everything in
• Research
• Lung transplantation

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Treatment burden

• The recommended treatment regimen is complex and
  becoming more so
• The median number of daily treatments is 7
  (nebulized and oral)
• Median time spent on all treatments is 108
  minutes
• Reported airway clearance treatments done by 49
  of adults
• Sawicki, G.S., Sellers, D.E., Robinson, W.M.
  2008.

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Now, on to the good stuff

• CF lung disease

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How old would you guess this patient is?
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CF Lung Disease
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Treating CF Lung Disease

• Therapies
• Frequent, high dose antibiotic use
• Chronic intermittent use of inhaled Tobramycin
• Aggressive airway clearancethis is not optional
  during inpatient stays
• Mucolytics (i.e., DNAse, 7 hypertonic saline)
• Bronchodilators
• Anti-inflammatory medications
• Ibuprofen
• Azithromycin
• Complications
• Respiratory failure
• Hemoptysis
• Spontaneous pneumothorax

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Nebulized treatments

• Albuterol
• Hypertonic saline
• Pulmozyme
• Inhaled antibiotics

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Nebulizers
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Airway clearance

• Chest Physiotherapy

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Vest
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More airway clearance techniques

• Active Cycle of Breathing deep breaths using
  diaphragm, then deep breath with hold, repeat and
  then huff
• Autogenic drainage deep breathing technique
  where patient exhales and then takes tidal volume
  breaths at lower level, and moves up the lungs

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Flutter
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PEP
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Acapella
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Age Specific Prevalence of Respiratory
Infections in CF Patients, 2006
100
P. aeruginosa
80
Any Staph
60
Percent of Patients
S. aureus
40
H. influenza
MRSA
20
B. cepacia
S. maltophilia
0
0 to 1
2 to 5
6 to 10
11 to 17
18 to 24
25 to 34
35 to 44
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Age (years)
P. aeruginosa 55.0
H. influenza 16.9
B. cepacia complex 2.9
S. aureus 51.5
S. maltophilia 12.6
MRSA 18.9
Any Staph 63.5 (S. aureus and/or MRSA)
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Inhaled antibiotics

• TOBI
• Colistin
• Aztreonam

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Other challenges

• Infection control
• Sterilizing equipment
• Hospitalizations
• Staying healthy
• Fitting everything in
• Research
• Lung transplantation

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Research
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Molecular Consequences of CFTR Mutations
Other classes have been proposed.81. Adapted
from Wilschanski M, et al. J Pediatr.
1995127(5)705-710. 2. Ratjen F. Curr Opin Pulm
Med. 200713(6)541-546.
3. MacDonald KD, et al. Pediatr
Drugs. 20079(1)1-10. 4. Suaud L, et al. Am J
Physiol Cell Physiol. 2007292(4)C1553-C1561.
5. Pedemonte N, et al.
Mol Pharmacol. 200567(5)1797-1807. 6. Sheppard
DN, et al. Nature. 1993362(6416)160-164.
7. Castellani C,
et al. J Cyst Fibros. 20087(3)179-196. 8. Rowe
SM, et al. N Engl J Med. 2005352(19)1992-2001.
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The newest of the new drugs

• Vertex Pharmaceuticals VX08
• Studies VX08-770-102 through 105
• The magic pill studies

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Other major issues for CF patients

• Medical insurance and coverage
• Cost of prescriptions
• Pulmozyme approximately 100/vial, taken once
  daily
• Childrens Specialty Health Program
• Idaho Health and Welfare, through the Idaho
  Legislature, aiming to cut the adult CF program

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Disability

• Social Security Disability Insurance
• Able to work under this program, eligibility base
  on amount of money the person has paid into
  Social Security

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• Disabled adults can get Social Security, but they
  can not be engaged in substantial gainful
  activity.
• Work hours very limited
• Research participation very limited
• The Cystic Fibrosis Foundation is working on this
  issue, since research is vital to a cure.

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Supplemental Security Income

• Also difficult to get
• Asset restrictions, includes spouses assets

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Other recommended reading

• Journal of Cystic Fibrosis 3 (2004) 237 242
• Journal of Cystic Fibrosis 8 (2009) 913
• Journal of Cystic Fibrosis 3 (2004) 814

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Websites

• www.cff.org
• Great tips here for how you can get involved!
• http//www.cystic-fibrosis-symptom.com/
• www.pulmozyme.com

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Thank you very much!

• Any questions?