Transcript of Diane Hanfelt-Goade MD Director, Adult CF Center.
- Slide 1
- Slide 2
- Diane Hanfelt-Goade MD Director, Adult CF Center
- Slide 3
- 28 year-old gentleman with cystic fibrosis, genotype F508
homozygous Diagnosed as an infant with meconium ileus Followed
every 3 months in CF clinic Colonization with Pseudomonas
aeruginosa and Staphylococcus aureus History of staph schleiferi
and aspergillus tares. Called with increasing cough and SOB for
three weeks
- Slide 4
- 1. Moderate to severe lung dysfunction 2.Pancreatic
insufficiency. 3.Chronic sinusitis, nasal polyps 4.Allergic
rhinitis. 5.Impaired glucose tolerance. 6.Reactive airway disease.
7.History of hiatal hernia. 8.History of H. pylori 9.Sleep apnea
10.Low body mass index.
- Slide 5
- 1.Pulmozyme 2.5 milligrams inhaled once daily. 2.7% hypertonic
saline inhaled once per day. 3.Oxygen 2 liters nocturnally. 4.Vest
once per day 5.Acapella once or twice per day. 6.Tobi 300
milligrams inhaled, 28 days on, 28 days off. This is an off cycle.
7.Aztreonam 75 milligrams inhaled three times a day 28 days on, 28
days off. 8.Azithromycin 500 milligrams by mouth Monday, Wednesday,
Friday. 9.Ultrase MT18s, 8-9 with meals and 4-5 with snacks.
10.Ensure three cans daily. 11.Multivitamin one tablet by mouth
once daily. 12.Calcium 600 milligrams with 125 of D, once daily.
13.Flonase 0.5 %, two sprays per nostril once or twice per day. 14.
AquADEK, 2 tablet by mouth daily 15.Scan Dical as needed.
16.Vitamin D 50,000 international units reports he took for 8 to 10
days 17.Vitamin A, dosage unknown, one tablet by mouth every day.
18.Vitamin E 400 international units one by mouth every day.
19.Zyrtec 10 mg by mouth as needed for allergies. 20. Spiriva 18
micrograms inhaled once daily. 21.Saline nasal washes as needed.
22.ProAir 90 micrograms inhaled two to three puffs prior to therapy
and as needed. 23.Advair HFA 2 puffs twice daily.
- Slide 6
- Pulmonary function tests FVC of 2.27 (39%), FEV1 1.30 (27%),
FEF 25-75% is 0.52 (11%), RV/TLC % of 46
- Slide 7
- A multisystem disease Autosomal recessive inheritance Cause:
mutations in the cystic fibrosis transmembrane conductance
regulator (CFTR) chromosome 7 codes for a c-AMP regulated chloride
channel Rosenstein, BJ and Zeitlin, PL. Cystic fibrosis. The
Lancet. 351: 277-82.
- Slide 8
- One or more clinical features of CF PLUS Two CF mutations on
genetic testing OR Two positive quantative pilocarpine
iontophoresis sweat chloride values OR An abnormal nasal
transepithelial potential difference value Cystic Fibrosis
Foundation. Clinical Practice Guidelines for Cystic
fibrosis.1997.
- Slide 9
- 1 st Descriptions 17 th Century European folklore A child that
tastes salty when kissed will soon die. Thought to be
hexed/bewitched 18 th Century Case Descriptions Cases of children
with severe malnourishment, steatorrhea, meconium ileus Quinton PM.
Phys Rev;1999;79:S3-S22. www.cysticfibrosismedicine.com
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- Clinical Description 1943 Dr. Stanely Farber Mucoviscidosis
Multisystem disease Major manifestations Chronic bronchopulmonary
infections Malabsorption and steatorrhea Growth Failure Farber S.
Arch Pathol 1944;37:283-250.
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- History 1948 Dr. Paul di Sant Agnese High chloride/sodium in
sweat CF patients Standardization of sweat test by 1959 1954 1st
comprehensive CF center
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- The CFTR gene is located on the long arm of chromosome 7. There
are 1522 mutations in CFTR listed on the mutation database
(http://www.genet.sickkids.on.c
a/cftr/)http://www.genet.sickkids.on.c a/cftr/ The most common
mutation is F508-70% CF alleles in caucasians. 1 Causes loss of aa
phenylalanine at position 508 in protein
http://www.ornl.gov/sci/techresources/
Human_Genome/posters/chromosome/cftr.shtml 1. Gibson, RL, Burns,
JL, and Ramsey, BW. Pathophysiology and Management of Pulmonary
Infections in Cystic Fibrosis. AJRCCM 168 (918-951); 2003.
- Slide 13
- Gibson, RL, Burns, JL, and Ramsey, BW. Pathophysiology and
Management of Pulmonary Infections in Cystic Fibrosis. AJRCCM 168
(918-951); 2003. CFTR functions as a regulated chloride channel
Also regulates the activity of other chloride and sodium channels
at the cell surface
- Slide 14
- Cilia do not beat well when PCL volume is depleted Mucins are
not diluted and cannot be easily swept up the airway Mucus becomes
concentrated Results in increased adhesion to airway surface
Promotes chronic infection Donaldson,SH and Boucher,RC. Update on
the pathogenesis of cystic fibrosis lung disease. Current Opinion
in Pulmonary Medicine. 9: 486-491; 2003.
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- Mucus---helps clear airway of bacteria Clearance of mucus
depends on Ciliary function Mucin secretion Volume of airway
surface liquid (ASL) Forms periciliary liquid layer Dilutes
mucus---facilates entrapment of bacteria and clearance Optimal
volume of ASL regulated by Na+ absorption and Cl- secretion
Donaldson,SH and Boucher,RC. Update on the pathogenesis of cystic
fibrosis lung disease. Current Opinion in Pulmonary Medicine. 9:
486-491; 2003.
- Slide 16
- Donaldson,SH and Boucher,RC. Update on the pathogenesis of
cystic fibrosis lung disease. Current Opinion in Pulmonary
Medicine. 9: 486-491; 2003.
- Slide 17
- Most common life-shortening recessive genetic disease in
Caucasians 1:3,500 newborns in the US 1 in 10,500 Native Americans
1 in 11,500 Hispanics 1 in 14,000 to 17,000 African Americans 1 in
25,500 Asians http://www.cff.org
- Slide 18
- About 30,000 people affected in United States >10,000,000
people carriers of mutant CFTR 80% cases diagnosed by age 3 Almost
10% diagnosed 18 years atypical disease UNM Adult care center has
approx 66 patients http://www.cff.org
- Slide 19
- Overall trend is improved survival Female survival worse than
male between 2-20 years of age 1 35% of patients are older than 18
years of age 2 Median survival 36.8 years 3 1930s life expectancy
was about 6 months 2 The impact of usual adult diseases in CF is
virtually unknown 1.Goss, CH and Rosenfeld, M. Update on cystic
fibrosis epidemiology. Current Opinion in Pulmonary Medicine.
10:510-514; 2004. 2. Davis, P. Cystic Fibrosis Since 1938.
AJRCCMss. Doi: 10.1164/rccm.200505-840OE; 2005.
3.www.cff.org/news/general_news
- Slide 20
- Chronic Sinusitis Chronic pulmonary infections Endobronchial
disease GI disease Nutritional deficiencies Liver disease CFRD,
pancreatic dysfunction Obstructive azospermia
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- Chronic infection with CF pathogens Endobronchial disease
Cough/sputum production Air obstruction---wheezing; evidence of
obstruction on PFTs Chest x-ray anomalies Digital Clubbing Sinus
disease Nasal Polyps CT or x-ray findings of sinus disease Cystic
Fibrosis Foundation. Clinical Practice Guidelines for Cystic
fibrosis.1997.
- Slide 22
- Hyperinflation Peribronchial cuffing Bronchiectasis Diffuse
fibrosis Atelectasis From: http://www.meddean.luc.edu/lumen/med
ed/elective/pulmonary/cf/cf_f.htm
- Slide 23
- Benign lesions in nasal airway If large enough, can be
associated with significant nasal obstruction, drainage, headaches,
snoring Likely associated with chronic inflammation May need
surgical intervention High recurrence rate From:
http://www.emedicine.com/http://www.emedicine.com/
ped/topic1550.htm
- Slide 24
- Intestinal abnormality Meconium ileus Distal intestinal
obstruction syndrome (DIOS) Rectal prolapse Hepatobiliary disease
Focal biliary cirrhosis Multilobular cirrhosis Pancreatic endocrine
dysfunction Cystic fibrosis related diabetes
- Slide 25
- Pancreatic insufficiency Autopsy of malnourished
infants--1938--- cystic fibrosis of the pancreas---mucus plugging
of glandular ducts 1 1.Davis, P. Cystic Fibrosis Since 1938. AJRCCM
Articles in Press. Doi: 10.1164/rccm.200505-840OE; 2005.
- Slide 26
- Chloride impermeability affects HCO3- secretion and fluid
secretion in pancreatic ducts 2 Pancreatic enzymes stay in ducts
and are activated intraductally Autolysis of pancreas Inflammation,
calcification, plugging of ducts, fibrosis Malabsorption Failure to
thrive Fat soluble vitamin deficiency 1.Davis, P. Cystic Fibrosis
Since 1938. AJRCCM Articles in Press. Doi:
10.1164/rccm.200505-840OE; 2005. 2. Quinton, P. Physiologic Basis
of Cystic Fibrosis. Physiol Rev 79:3-22, 1999.
- Slide 27
- Complications Endocrine Glucose intolerance/CFRD Reduction in
insulin secretion due to pancreatic damage Insulin resistance
related to infection and CF exacerbations Associated with
accelerated pulmonary decline and increased mortality Arthropathy
(2-9%) Osteopenia/osteoporosis
- Slide 28
- Focal inspissation of bile Obstructs biliary ductules Second
leading cause of death in CF 1 Prevalence 9-37% 1 Spectrum of
disease increased liver enzymes biliary cirrhosis portal
hypertension 1. Efrati, O et al., Liver Cirrhosis and portal
hypertension in CF. European Journal of Gastroenterology and
Hepatology. 15(10): 1073-1078; 2003.
- Slide 29
- Clinically---hypochloremic metabolic alkalosis CFTR on luminal
side of sweat duct Chloride goes in from lumen via CFTR and out to
blood by other transporters Sodium goes in via ENaC Defective
CFTR---Na and Cl- movement and reabsoprtion into lumen impeded
Goodman, B and Percy, WH..CFTR in Teaching Membrane Transport. Adv
Physiol Educ. 29 (79-82); 2005
- Slide 30
- Pathophysiology Murphy TM and Rosenstein BJ Genetic and Protein
Defect Abnormal Salt and Water Transport Persistent Airway
Infection, invasion of neutrophils Accumulation of
Leukocyte-Derived DNA and Elastase-Rich Secretions Exacerbations of
Infections Airway Obstruction Progressive Lung Destruction Early
Death
- Slide 31
- Modify phenotype and disease expression in CF TGF-beta 1 potent
suppressor of T cell activation can decrease T cell proliferation
and cytokine production In a study of 808 patients w delta F 508
mutation, polymorphisms in the TGF-beta 1 gene were associated with
more severe CF lung disease MBL Mannose-binding lectin important
component of the complement system deficiencies increase the risk
for pyogenic infections In CF, variant MBL alleles associated with
reduced lung function, increased risk for complex infections, and
early death polymorphisms of TNF-a increase susceptibility to Ps.
aeruginosa infection and contribute to the clinical manifestations
of CF
- Slide 32
- Individuals with CF are living longer most common cause of
death in CF is respiratory failure secondary to pulmonary
infection. Pseudomonas aeruginosa and Burkholderia cepacia complex
are the pathogens most commonly associated with a shortened life
span With prolonged infection, P. aeruginosa converts to a mucoid
phenotype by the production of alginate Conversion to mucoidy is
associated with worsening lung function increase in the prevalence
of several potentially pathogenic microorganisms in CF
- Slide 33
- Gibson, RL, Burns, JL, and Ramsey, BW. Pathophysiology and
Management of Pulmonary Infections in Cystic Fibrosis. AJRCCM 168
(918-951); 2003.
- Slide 34
- B. cepacia syndrome: fevers, rapidly progressive necrotizing
pneumonia, death Chronic cepacia infection decreased lung function
and increased mortality Several closely related species termed
genomovars 1 III has been associated with more severe disease
Holmes, A, Govan, J, and Goldstein, R. Agricultural Use of
Burkholderia (Pseudomonas) cepacia: A Threat to Human Health?
Emerging Infectious Diseases. 4(2):221-227; 1998 1. Gibson, RL,
Burns, JL, and Ramsey, BW. AJRCCM 168 (918-951); 2003.
- Slide 35
- NTM in about 13% of patients 75% is MAC Treat if criteria for
disease is met: pulm nodules, deteriorating function Aspergillus
Infection vs. colonization ABPA Nationwide, MRSA increased from 2.1
percent in 1996 to 21.2 percent in 2007
- Slide 36
- Increased cough Increased sputum production or chest congestion
Increased dyspnea with exertion Increased fatigue Decreased
appetite Increased respiratory rate or dyspnea at rest Change in
sputum appearance Fever (present in a minority of patients)
Absenteeism from school or work Increased nasal congestion or
drainage Reductions in FEV1 Reduction of greater than 10% =
admission
- Slide 37
- Admitted for 14 days antibiotics chest phsyiotherapy and
inhaled meds 4 times daily Aggressive nutrition, physical therapy
Blood sugar control After 14 days of treatment, patients receiving
antibiotics had greater increases in several pulmonary function
measures than those treated with placebo Standard of care, so
covered by most insurances Majority of patients with some second
payer coverage
- Slide 38
- Directed to culture results Recognize that multiple species
often present We are now using synergy data as well Most common:
tobra + anti-PA ES PCN (zosyn) or 3 rd or 4 th gen ceph The
clearance of aminoglycosides is accelerated in CF patients Once
daily dosing endorsed by the CFF Patients hypermetabolic, increased
hepatic clearance of sulfonamides No changes: vanco, quinolones ?
Absorption of oral antibiotics
- Slide 39
- 18 months: data on 65 patients with at least one positive
culture Most with persistent positive cultures Most with
polymicrobial infections 52 PA 90% mucoid Increasing MDRO now
almost 50% 18 MSSA and PA 5 MRSA and PA
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- 23 MSSA 14 MRSA 2 B. cepacia patients MSSA, PA, B. cepacia
MRSA, B. cepacia Aspergillus fumigatus, B. cepcia 4
Stenotrophomonas 1 small colony variant 4 H. flu
- Slide 41
- Kleb pneumo Flavobacterium meningosepticum Achromobacter
Morganella Aspergillus fumigatus Aspergillus terus Scedosporium
apiospermum Nocarida transvalensis R to bactrim
- Slide 42
- CF Foundation guidelines UNM is a certified care center
Certification requires demonstration of an integrated team approach
Compliance with guidelines and standards of care Standards
developed using evidence based care practices, committee review
Current guidelines and supporting data at the CF Foundation website
http://www.cff.org/treatments/CFCareGuidelines
- Slide 43
- Diane Hanfelt-Goade, adult clinic director Charles Gallegos
CFNP, CF care specialist Linda Reineke, nutritionist and diabetes
educator Bill Demary, resp therapy Felisha Martinez, social
work
- Slide 44
- A systematic review was performed addressing a series of
questions related to treatment of pulmonary exacerbations. For each
question, the body of evidence was evaluated by the full Committee.
Recommendations were drafted using the U.S. Preventive Services
Task Force (USPSTF) grading scheme, which provides a mechanism to
weigh the quality of evidence and the potential harms and benefits
in determining recommendations (Table 1) Cystic Fibrosis Pulmonary
Guidelines: Treatment of Pulmonary Exacerbations Patrick A. Flume1,
Peter J. Mogayzel, Jr.2, Karen A. Robinson3, Christopher H. Goss4,
Randall L. Rosenblatt5, Robert J. Kuhn6, Bruce C. Marshall7, and
the Clinical Practice Guidelines for Pulmonary Therapies Committee*
Am. J. Respir. Crit. Care Med. 2009 Nov;180(9):802-8. Epub 2009
Sept. 3
- Slide 45
- Although they did not meet criteria for this systematic review,
there are observational studies that suggest better outcomes for
patients treated in a hospital than for those treated at home (10,
11). If there is any doubt, admission to the hospital is the
suggested option. This may be particularly relevant for patients
with comorbidities that complicate care and for patients with more
severe exacerbations who may be too fatigued or in too much
distress to be able to perform the therapies adequately. For
example, nutritional needs, elevated in most patients with CF, are
even greater during an exacerbation (8)
- Slide 46
- Chest physiotherapy Postural drainage and percussion P.E.P
valve, Acapella valve, Flutter valve High frequency chest wall
oscillation Albuterol Bronchodilation Increase ciliary efficiency
Dornase alpha/recombinant DNase (pulmozyme) Breaks down excess DNA
from neutrophils and bacteria Hypertonic Saline by nebulization
Thins secretions
- Slide 47
- Saiman et al., 2003 double blind placebo controlled trial of
azithromycin 185 patients randomized to receive 3 times weekly
azithromycin or placebo Improvements in lung function, weight, and
number of pulmonary exacerbations (decreased courses of antibiotics
and days in hospital) Saiman et al., Azithromycin in Patinets with
Cystic Fibrosis Chronically Infected with Pseudomonas Aeruginosa.
JAMA 290(13):1749; 2003.
- Slide 48
- Follow nutrition parameters closely Pancreatic enzymes Vitamin
supplementation Fat soluble vitamins ADEK daily Other nutritional
supplementation Tube feedings High calorie supplemental shakes,
formulas
- Slide 49
- Initiate if have malabsorption history Fecal fat Fecal elastase
May need H2 blocker or PPI to activate enteric coated enzyme
Enzymes with meals and snacks, usually keep at bedside Patients
bring their own, as hospital typically does not carry the branded
enzymes Fibrosing colonopathy Strictures in the colon associated
with high dose enzyme use (enzyme gets to colon and causes damage
leading to scarring/stricture)
- Slide 50
- Ursodiol Increased bile flow Decrease toxicity of bile acids
Sclerotherapy, portosystemic shunts Liver transplantation---only
curative treatment for portal hypertension
- Slide 51
- Quality of life Frequent hospitalizations Time spent on
therapies Morbidity from disease Restrictions secondary to disease
Adherence to therapies Family planning End of life issues
- Slide 52
- CF is a genetic disorder that most commonly results in chronic
pulmonary infections and issues related to pancreatic insufficiency
Ultimately, the majority of patients still die from respiratory
failure due to chronic infections Appropriate treatment is complex
and requires a team approach
- Slide 53
- Lack of knowledge/info on CF specific care Currently, CF
survival guide on drop down menu in CF order set interns/residents
should use the CF checklist and survival guide this should become
available on the Hospitalist Wiki? Standard order sets for
admission may not apply DVT prophylaxis should not be used as a
matter of course Patients on daily vit K therapy Patients at much
higher risk for hemoptysis or bleeding than for clotting - CF DM
educator should take point on CF DM Routine insulin orders
generally not applicable, CFRD different than type 1 DM Endo
consult appropriate for anyone on a pump
- Slide 54
- We should define a clear procedure for admission of CF "tune
ups May be several days before a bed available CF team always
contact admitting team Information not always passed along CF team
always dictates a stat note with reason for admission, order recs
Lack of communication on inpatients Charles rounds with pulmonary
team daily Charles discusses patients with Diane daily Entire CF
team rounds wed afternoon ? Should we round with medicine teams
once a week also, or after an admission Resident or Intern should
contact Charles to arrange a good time, Monday?