Term
an autosomal recessive genetic disease that results in faulty transport of salt in organs
multi-system disease:
respiratory system - cycle of lung infection or exacerbation and inflammation which slowly damages lungs, eventually impairing ability to provide O2 to the body
digestive system - pancreas is affected, causes problems with digestion, making it difficult to grow normally and keep a healthy body weight
endocrine system
bone and joint
reproductive system
CFRD (CF related diabetes) - pancreas unable to secrete insulin and insulin resistant
depression
leads to thick, sticky mucus that blocks the ducts of these organs, disrupting their normal functions |
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Definition
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Term
Caucasians > Hispanic, African American
most common life shortening genetic disorder in Caucasians
female = male |
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Definition
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Term
2 copies of abnormal gene must be present for disease
inherited through the non-sex chromosomes from both parents that are carriers:
25% chance of disease, 50% chance of carrier, 25% chance of non-carrier
1 parent = child carrier |
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Definition
| what does autosomal recessive mean? |
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Term
improved survival in CF
[image] |
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Definition
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Term
2 base pair deletion on chromosome 7
this sequence codes for CFTR (CF transmembrane conductase receptor)
there are over 1800 known mutations of the CF gene |
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Definition
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Term
CFTR regulates Na, Cl, and water transport in epithelial cells
this protein acts as a cAMP mediator of Cl channel conductance in epithelial cells
it regulates Na, Cl, and secondarily water transport across cell membranes which are responsible for creating airway surface liquid necessary for effective mucociliary clearance
in CF, genetic mutations lead to defective CFTR production, processing, conductance, and/or regulation
as a result of the CFTR mutation, epithelial cells are unable to secrete Na and Cl, and water is reabsorbed into the cell
this defect occurs in epithelial cells of the respiratory, hepatobiliary, gastrointestinal, and reproductive tracts along with the pancreas and sweat glands
dehydrated and viscous secretions are ineffectively cleared and cause luminal obstruction, scarring, and dysfunction |
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Definition
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Term
CF PANCREAS
Chronic cough
Failure to thrive
Pancreatic insufficiency
Alkalosis
Neonatal intestinal obstruction/Nasal polyps
Clubbing/CXR findings
Rectal prolapse
Electrolyte abnormalities
Absence of vas deferens/pulmonary cilia
Sputum |
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Definition
| clinical presentation of CF |
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Term
neonatal screenings: increased immunoreactive trypsinogen (IRT)
clinical features of CF PLUS:
1) sweat chloride test - need 2 positive tests to confirm CF
OR
2) genotyping - +1500 CFTR mutations identified; need 2 known CFTR mutations to confirm CF
5 months is median age at diagnosis, 60% are diagnosed by 1 year of age and 90% by 5 years, but trend will likely continue to decrease
these tests do not identify severity |
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Definition
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Term
| defective Cl transport and enhanced sodium absorption |
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Definition
| CF results from a defect on chromosome 7 that affects the gene that codes for the protein known as CFTR in the lungs, impaired CFTR function causes: |
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Term
defective CF gene
defective/deficient CFTR
abnormal airway surface:
treated with hypertonic saline
bronchial obstruction:
thick mucus results in air trapping, bronchiectasis, atelectasis (results in COPD-like disease)
treated with airway clearance, dornase alfa, hypertonic saline
infection:
increased risk due to thick mucus acting as an excellent growth medium for microorganisms
treated with TOBI, azithromycin, oral/IV antibiotics
inflammation:
bacterial progression leads to elevated levels of inflammatory mediators (TNF-a, IL-1, IL-2, neutrophil elastase); further thickening of mucus and reduced efficacy of antibiotics; progressive airway and lung damage
treated with corticosteroids, ibupofen
bronchiectasis:
treated by lung transplantation |
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Definition
| pathogenesis of lung disease in CF |
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Term
cough/sputum production
wheeze, air trapping
radiographic abnormalities
evidence of obstruction on PFTs (FEV1 will decrease)
digital clubbing
nasal polyps |
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Definition
| common respiratory findings in CF |
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Term
MILD
FEV1 > 70-89% predicted
MODERATE
FEV1 40-69% predicted
SEVERE
FEV1 < 40% predicted |
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Definition
| CF disease severity: pulmonary impairment |
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Term
[image]
major improvement in lung function of people with CF since 1990
[image]
The rising number of people with mild disease and the dropping number with severe disease show that the lungs of people with CF are healthier now than 20 years ago |
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Definition
| CF lung function comparison from 1990s to current |
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Term
initial infections:
Staphylococcus aureus
Haemophilus influenzae
Streptococcus pneumoniae
colonization:
Pseudomonas aeruginosa
Burkholderia cepacia
Stenotrophomonas maltophilia
age 0-17 years most common pathogen = Staph
age 18 and up most common pathogen = P. aeruginosa |
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Definition
CF infection etiologies
initial infections, colonizations, and most prevalent organisms by age |
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Term
symptoms:
increased frequency and duration of cough
increased sputum production
change in appearance of sputum
shortness of breath
decreased exercise
decreased appetite
increased congestion in chest
signs:
increased RR
intercostal retractions
decrease in pulmonary function consistent with obstructive airway
fever and leukocytosis
weight loss
new infiltrates
[image]
frequent exacerbation more common in adolescents/young adults |
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Definition
| signs and symptoms of an acute pulmonary exacerbation in CF |
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Term
exercise
hydration
breathing techniques - belly breathing; "huff" breathing
conventional chest physiotherapy (CPT) - percussion with cupped hand/vibrator; postural drainage
oscillating positive expiratory pressure devices
high-frequency chest wall oscillation |
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Definition
| airway clearance therapy for CF |
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Term
oral penicillins and cephalosporins
dicloxacillin, cephalexin |
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Definition
| antimicrobial therapy for an initial infection in CF |
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Term
COMBINATION anti-pseudomonal therapy
duration: 14-21 days
synergistic activity
slow development of resistance
ceftazedime PLUS AG (tobramycin)
piperacillin PLUS AG (tobramycin)
other anti-pseudomonals:
aztreonam
CIPROFLOXACIN
meropenem
ticarcillin/clavulanate
FQs are the ONLY ORAL ANTIBIOTIC TO TREAT PSEUDOMONAS!
can use FQs in children (ciprofloxacin) in cases of CF |
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Definition
| antimicrobial therapy for a pseudomonal infection in CF |
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Term
vancomycin
linezolid
bactrim
clindamycin not effective in CF b/c MRSA is similar to hospital acquired |
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Definition
| antimicrobial therapy for MRSA infection in CF |
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Term
adjunct to antibiotics for treatment
home maintenance therapy
improved drug delivery to site of infection
reduced systemic exposure
ADRs: increased cough, hoarseness
no products approved for exacerbation treatment, usually used as maintenance; chronic therapy every other month
concern for emerging resistance? |
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Definition
| role of aerosolized antimicrobial therapy in CF |
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Term
TOBI (tobramycin)
criteria: >/= 6 years + P. aeruginosa
dosed: BID alternating months
benefits: increases FEV1 ~10%, decreases hospital days/IV antibiotics
Cayston (aztreonam)
same criteria
dosed: TID alternating months
benefits: increases FEV1 ~10%, decreases symptoms
only available at CF specialty pharmacies |
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Definition
| examples of aerosolized antimicrobial therapy |
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Term
prevent/delay colonization with CF pathogens:
Staphylococcus aureus
Pseudomonas aeruginosa: TOBI, macrolides
Stenotrophomonas maltophila: SMX/TMP
PROPHYLAXIS NOT ROUTINELY RECOMMENDED AT THIS TIME |
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Definition
| antimicrobial prophylaxis in CF |
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Term
MOA:
reduces sputum viscosity
cleaves DNA in sputum reducing sputum viscosity and/or its adherence to epithelial airways improving mucociliary sputum clearance and lung function
Critera: >/= 6 years
Dosing: given after SABA
benefits:
decreases pulmonary exacerbations
decreases IV antibiotic use
increases FEV1 by 5%
ADRs:
hoarseness
pharyngitis |
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Definition
Pulmozyme (dornase alfa)
MOA, criteria, benefits, ADRs |
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Term
osmotic agent that increases the water content of the airway surface liquid and improves clearance of mucus
thins mucus
induces expectoration
FEV1 increased from baseline by 7%
routine use not recommended |
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Definition
Mucomyst (N-acetylcysteine)
MOA |
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Term
mobilize sputum
controversial benefits
adjunct therapy to conventional chest physiotherapy (CPT)
use prior to/during airway clearance with saline
ADRs: jitteriness, dose dependent
recommended for patients >/= 6 years with + bronchodilator response |
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Definition
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Term
used for reactive airway disease
concern for toxicity
reserved ONLY for patients with documented improvement |
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Definition
| role of theophylline in CF |
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Term
glucocorticoids:
little role in long-term therapy
concern for ADRs
high dose ibuprofen:
ADRs - GI, nephrotoxicity
concern for intermittent low dose
macrolides:
azithromycin
criteria - >/= 6 years, weight > 25 kg, FEV1 > 30% predicted, no B. cepacia present, no liver disease
benefits - increases FEV1 ~6%, decreases hospital stays/IV antibiotics, weight gain |
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Definition
| anti-inflammatory agents used in CF |
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Term
increases mucociliary clearance
criteria: >/= 6 years
dosed after SABA
benefits: increase sputum clearance to increase lung function, decreases exacerbations, decreases IV antibiotics
ADRs: coughing, sore throat, chest tightness |
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Definition
| role of hypertonic saline in CF |
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Term
A: Strong recommendation for:
inhaled tobramycin - moderate to severe disease
dornase alfa - moderate to severe disease
B: recommended for:
inhaled tobramycin - asymtpomatic to mild disease
dornase alfa - asymtpomatic to mild disease
hypertonic saline
ibuprofen
macrolides
inhaled B-agonists
D: recommendation against:
oral corticosteroids - age 6 to 18 years
inhaled corticosteroids
anti-Staph antibiotics |
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Definition
summary of recommendations for pulmonary treatment of CF
A, B, and D recommendations |
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Term
caused by Pseudomonas, H. flu, Strep, and/or anaerobes
25-50% of patients may develop nasal polyps
treat with topical steroids or antihistamines for allergic symptoms
requires surgical removal
immunization |
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Definition
| treatment of sino-pulmonary disease in CF (pansinusitis) |
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Term
exocrine pancreatic insufficiency
fat-soluble vitamin deficiency
meconium ileus
distal intestinal obstruction disorder
rectal prolapse
gastrointestinal reflux
recurrent pancreatitis
hepatobiliary disease
failure to thrive
hypoproteinemia-edema |
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Definition
| gastrointestinal/nutritional abnormalities of CF |
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Term
increased caloric requirements (130-150% of RDA for age)
oral supplements: Ensure, Scandishakes
enteral feedings: nocturnal feedings
pharmacologic agents: not routinely recommended
anabolic agents - growth hormone, megestrol acetate
cyproheptadine |
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Definition
| nutritional management in patients with CF |
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Term
about 90% of people with CF have pancreatic insufficiency
role: achieve adequate nutrition, abolish GI symptoms, achieve normal bowel function
agents vary in amylase:lipase:protease ratios - NOT bio-equivalent, NOT interchangeable |
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Definition
| role of pancreatic enzyme replacement therapy in patients with CF |
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Term
dose based on LIPASE activity
individualize dose, titrate to response
take before each meal or snack |
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Definition
| dosing of pancreatic enzyme replacement therapy |
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Term
fat soluble vitamin replacement:
Vitamin A
Vitamin D
Vitamin E
Vitamin K
monitor vitamin A, D, E levels yearly
beta-carotene
calcium
iron
zinc
sodium
TAKE WITH ENZYME |
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Definition
| vitamin/mineral/electrolyte supplementation in patients with CF |
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Term
decreased bicarbonate secretion, gastric acid cause decreased absorption of pancreatic enzymes
antacids
histamine-2 receptor antagonists
proton pump inhibitors
gastroesophageal reflux:
above +/- metoclopramide (Reglan) |
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Definition
| gasterointestinal therapy for patients with CF |
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Term
delay the progression of lung disease
normal nutrition, growth, and development
normal bowel habits
reduce pulmonary symptoms |
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Definition
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Term
ursodiol
role: improves bile flow, displaces toxic bile acids that accumulate in liver disease |
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Definition
| treatment of cholestasis/fibrosis/cirrhosis sequence in patients with CF |
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Term
| propranolol for prophylaxis and variceal bleeding |
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Definition
| treatment of cirrhosis induced portal hypertension in patients with CF |
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Term
prevalence 22%
primary cause is insulin deficiency
age of onset: 18-21 years
individualized insulin regimen:
split dose NPH/regular insulin
lispro before meals/lantus HS
insulin pump therapy
microvascular complications can occur
> 10 years should be tested for CFRD, diagnosing and treating CFRD earlier results in better outcomes |
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Definition
CF related diabetes
onset and therapy |
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Term
weight bearing exercise
avoid tobacco, alcohol, caffeinated/carbonated beverages
calcium
vitamin D
vitamin K, magnesium, zinc, copper |
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Definition
| treatment of CF bone disease |
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Term
regular visits quarterly
annual visit:
multidisciplinary approach
history and physical
laboratory measurements
sputum/throat swab culture
spirometry
oral glucose tolerance test/DEXA
education |
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Definition
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Term
Increased pulmonary vascular resistance
Fixed pulmonary vascular obstruction
Cor pulmonale and CHF
Patients with FEV1 <30%, PaO2 <50mm Hg or PCO2 >50 mm Hg have about a 50% chance of surviving 2 years
Lung transplant is very risky and the supply of good lungs for transplant is limited |
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Definition
| progression of CF lung disease |
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Term
gene therapy:
correction of the genetic defect by administering of right DNA sequence into airway epithelial cells
research involving appropriate vector for delivery underway - viral vectors, non-viral vectors
protein therapy:
correction of function of defected CFTR
research involving appropriate CFTR modulation underway |
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Definition
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Term
absorption:
increased gastric acid secretions
lower duodenal pH
insufficient pancreatic enzymes, loss of bile acid
distribution:
increased extracellular fluid/decreased fat mass
altered protein binding
increased Vd for water soluble drugs
decreased albumin, decreased binding affinity for protein bound drugs
metabolism (hepatic)
cirrhosis, cholestasis
increased fecal loss of bile acids
increased acetylation
elimination:
increased renal clearance for impaired tubular reabsorption
enhanced tubular secretion |
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Definition
| pharmacokinetic considerations for patients with CF |
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Term
albuterol -> hypertonic saline -> pulmonzyme -> TOBI/Cayston
DO NOT MIX solutions |
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Definition
| sequence of nebulizer solutions |
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