Cystic Fibrosis: Where Are We At?
Joseph G. Sorbello, MSEd, RT, RRT
Associate Professor and Chair
Department of Respiratory Therapy Education
College of Health Professions
SUNY Upstate Medical University
Syracuse, N.Y.
Conflict of Interest
I have no real or perceived conflict of
interest that relates to this presentation. Any
use of brand names is not in any way meant
to be an endorsement of a specific product,
but to merely illustrate a point of emphasis.
Cystic Fibrosis
lethal autosomal recessive disease
 incidence: 1 in 2000-3000; predominantly Caucausian populations
(carrier frequency 1 in 22-28)
disease gene CFTR (cystic fibrosis transmembrane conductance regulator)
is a regulated epithelial Cl- channel; influences other ion channels
“Woe to the child which when kissed on the forehead
tastes salty. He is bewitched and soon will die” - old proverb
Cystic Fibrosis
Normal lung (top left) Cystic fibrosis (CF) patient (top right) showing an enormous number of ectatic lesions (arrows) with most airways completely filled and
obstructed with purulent mucoid accumulations (black arrows). Examined microscopically, the lumens of normal small airways are virtually free of secretions
(bottom left); in contrast, bronchioles from a CF patient can be obstructed and distended by mucus with no inflammation (bottom right).
• Cystic Fibrosis is an inherited
disease.
• For a child to inherit CF, both
parents must be carriers of a
defective gene on chromosome 7.
- They then have a 50% chance of
becoming a carrier.
- A 25% chance of getting CF
- A 25% chance of not being a carrier
and not having CF
Think Globally!
It affects the…
Lungs
Pancreas
• Mucus builds up and obstructs
airways
• Pancreas produces enzymes that help
with digestion
• Build up also makes a suitable
environment for bacterial growth
• Build up of mucus blocks ducts in
pancreas, stopping enzymes form reaching
intestines
Bacterial growth increases risk of
infections
Repeated infections cause lung
damage
Without enzymes, intestines can’t digest
food properly
Leads to loss of vitamins and nutrients
 Persistent cough, often with sputum or possibly blood streaking
 Difficulty breathing / wheezing
 Fatigue
 Fleshy growths inside the nose (nasal polyps)
 Weight loss / poor weight gain → “failure to thrive”
 Frequent lung infections, pneumonia, bronchitis
 Abdominal pain
 Salty tasting skin (salt loss when sweating) leading to dehydration
 Greasy, light colored, foul smelling stools or diarrhea
What therapies do we have?
Airway clearance techniques:
- Coughing, huff coughing
- CPT/Pd
- Oscillatory PEP: FlutterTM, AcapellaTM, CornetTM
- High Frequency Chest Oscillation (Vest or Oscillator)
- PEP Therapy
- Active Cycle of Breathing Technique (ACBT): breathing control, thoracic
expansion, forced expiratory technique
- Autogenic Drainage (“self drainage”): dislodging, collecting and clearing
mucus
What therapies do we have?
What procedural order is recommended sequence for inhaled
medication and respiratory therapies?
According to the Cystic Fibrosis Foundation panel of experts:
1. Bronchodilators (Albuterol, Combivent™, Xopenex™) to open the airways
2. Hypertonic Saline (7%) to mobilize mucus and improve airway clearance with
*Airway Clearance Technique: Vest, Flutter™, Chest PT, IPV, etc. (listed after
Pulmozyme, however it’s recommended to always make sure that an aerosol is
delivered during Vest Therapy)
3. Pulmozyme™ (DNAse) to thin mucus (recommended to wait 20 minutes then…..
4. Antibiotics (TOBI™, Colistin, Cayston). The previous therapies open and clear the
airways of mucus, allowing these antibiotics to work on remaining bacteria.
5. Steroids (Flovent™, Pulmicort™, QVAR™)
Directions for patients
If coughing up blood, temporarily stop Pulmozyme™, saline, airway
clearance technique, and inhaled antibiotics. Call your CF doctor or
respiratory therapist for further advice.
With a respiratory illness or change in symptoms:
-Begin or increase airway clearance techniques.
-Use breathing treatments as ordered; use bronchodilators
every three to four hours, and often additional Vest and/or
hypertonic saline treatments are useful.
Contact your CF doctor or respiratory therapist to see if antibiotics
or additional intervention is needed.
What therapies do we have?
Am J Respir Crit Care Med 2009 Vol 180. pp 802–808
What therapies do we have?
Medications:
- Hypertonic Saline (7%, aerosol)
- TOBI® (inhaled tobramycin)
Alternate q 28 days
- Cayston ® (aztreonam for inhalation solution)
- Zithromax® (azithromycin)
- Pulmozyme ® (dornase alfa)
- Kalydeco: pill, > 6 years-old with certain gene mutations
- Ibuprofen ® (Advil ®, Motrin ®, Midol ®, NeoProfen ®, Caldolor ®
Access:
- PICC (Peripherally Inserted Central Catheter)
- Implanted port
What therapies do we have?
- Cayston ® (aztreonam for inhalation solution; old term: AZLI)
*Use the Altera Nebulizer system
What therapies do we have?
Nutrition:
Infants
-Higher weight gain is good! Get to normal range and stay there
-Breast milk or infant formula best in first year
-Extra calories if behind in weight (consult dietician)
-After year, check with dietician for whole milk and/or supplement
-AAP suggests solid food addition when baby is ready (usually 4-6
months of age→single-grain cereal, strained fruits, balanced diet
-Extra calories often needed (dietician) then progression as with
other children
-Vitamins (ADEK)
-Enzymes (physician & dietician)
-Na+ especially in hot weather
-Tube feeding (if necessary, last resort)
What therapies do we have?
Nutrition:
Toddler (1-3 years-old)
-mealtime shorter than infant
-get calories eaten in first 10-15 minutes
-avoid foods causing choking (meat, hot dogs, raw fruits & veggies,
-Most need 1,000-1,300 calories/day but CF probably 1,3001,900/day
-Enzymes (physician & dietician)
-Extra calories often needed (dietician) then progression as with
other children (finger and spoon-thick foods)
-Vitamins (ADEK)
-Na+ especially in hot weather
What therapies do we have?
Nutrition:
Teens (13-19 years-old)
- Caloric need 30-50% more than ordinary teens so it’s 3,000 – 5,000
calories/day, with 600-1,000 calories from protein
- More iron needed during puberty (also Ca+, PO4, Mg, Fluoride
- More calcium needed also: 1,300 mg/day → milk/milk products
- Enzymes (physician & dietician)
- Extra calories often needed (dietician) then progression as with
other children (finger and spoon-thick foods)
- Vitamins crucial (ADEK)
- Na+ especially in hot weather
- High calorics: high energy lunches, snacks, milkshakes,
supplements
- Balanced diet
-Feeding tubes if necessary
-Diabetes (check blood glucose > 10 years-old)
-Exercise
What therapies do we have?
Nutrition:
Adult and all
-Encourage and practice healthy eating habits & lifestyle
-Vitamins & Minerals
-Bone health: CF patients prone to both osteoporosis and
osteopenia →avoid certain meds: e.g. steroids, Depo-Provera (birth
control), Megace (increases appetite),
immunosuppresants, antacids containing aluminum,
herbal medicines and “natural supplements”
CF Care Guidelines
What guidelines are available?
Guidelines for CF care are available here, along with
the supporting information from scientific journals and
medical meetings that provided the basis for the
Foundation’s guidelines. The available guidelines
include:
Diagnosis
CF Diagnosis
Sweat Testing
Newborn Screening
CFTR Metabolic Syndrome (CRMS)
Nutrition/GI
Nutrition in Children and Adults (2008)
Pancreatic Enzyme Replacement
Cystic Fibrosis-related Diabetes (CFRD)
Vitamin D
Bone Health
Liver Disease
Pediatric Nutrition (2002)
http://www.cff.org/treatments/CFCareGuidelines/
CF Care Guidelines
What guidelines are available?
Respiratory
Chronic Medications for Lung Health
Maintenance
CF Airway Clearance Techniques
Exacerbations
Pulmonary Complications
ABPA
Lung Transplants
Infection Control
Age-Specific Care
Infant Care
CFTR Metabolic Syndrome (CRMS)
Adult Care
Antioxidants
References
http://www.cff.org/treatments/CFCareGuidelines/
Infection Prevention and Control Guideline for Cystic Fibrosis: 2013 Update
Infection Control and Hospital Epidemiology August 2014, vol. 35, no. S1
Since 2003, new knowledge and new challenges provided the following rationale to
develop updated IP&C strategies for this unique population:
1.
The need to integrate relevant recommendations from evidence-based
guidelines published since 2003 into IP&C practices for CF. These included
guidelines from:
New evidence leads us to renewed emphasis on source containment of potential
pathogens and the role played by the contaminated healthcare environment
in the transmission of infectious agents.
And an increased understanding of the importance of the application of
implementation science, monitoring adherence, and feedback principles has been
shown to increase the effectiveness of IP&C recommendations
Since 2003, new knowledge and new challenges provided the following rationale to
develop updated IP&C strategies for this unique population:
2. Experience with emerging pathogens in the non-CF population has expanded our
understanding of droplet transmission of respiratory pathogens and can inform
IP&C strategies for CF.
These pathogens include severe acute respiratory syndrome coronavirus and the 2009
influenza A H1N1. Lessons learned about preventing transmission of methicillin
resistant Staphylococcus aureus (MRSA) and multidrug-resistant gram-negative
pathogens in non-CF patient populations also can inform IP&C strategies for CF.
And an increased understanding of the importance of the application of
implementation science, monitoring adherence, and feedback principles has been
shown to increase the effectiveness of IP&C recommendations
Since 2003, new knowledge and new challenges provided the following rationale to
develop updated IP&C strategies for this unique population:
3.
As the use of molecular technologies increased throughout the past decade, there
is an improved understanding of the epidemiology of newer CF pathogens that
are increasing in prevalence and are associated with increased morbidity
and mortality.
Such pathogens include MRSA, Mycobacterium abscessus, new species in the
Burkholderia cepacia complex (e.g., Burkholderia dolosa), and epidemic clones of
Pseudomonas aeruginosa (eg, the Liverpool epidemic strain).
The key recommendations in this document that are
new for the CF community are as follows:
1.
Develop strategies to monitor adherence to Infection Protection and Control
(IP&C) practices by healthcare personnel and provide them with feedback
for improvement.
2.
Partner with IP&C teams to implement the recommendations in this guideline,
especially those that are likely to be followed in areas of the facility that are not
dedicated only to people with CF.
3.
Implement Contact Precautions (ie, wear a gown and gloves) when caring for all
people with CF, regardless of respiratory tract culture results, in both ambulatory
and inpatient settings.
The key recommendations in this document that are
new for the CF community are as follows:
4.
Separate all people with CF from others with CF, regardless of their respiratory
tract culture results, at least 6 feet (2 meters) in all settings, to reduce the risk of
droplet transmission of CF pathogens.
5.
All people with CF and their family members and friends should perform
appropriate hand hygiene (with either alcohol-based hand rub or antimicrobial
soap and water) when there is the potential for contamination of hands with
pathogens. Contamination of hands may occur when entering and exiting a CF
clinic, clinic exam room, or hospital room or from respiratory secretions after
coughing, performing pulmonary function tests, or performing chest physiotherapy.
6.
All people with CF, regardless of respiratory tract culture results, should wear a
surgical (also called procedure or isolation) mask when in a healthcare setting to
reduce the risk of transmission or acquisition of CF pathogens.
The key recommendations in this document that are
new for the CF community are as follows:
7.
Perform pulmonary function tests (PFTs) to reduce transmission from one person
with CF to another person with CF by performing the test in one of the following
ways:
• In the exam room at the beginning of the clinic visit, allowing 30 minutes to
elapse between CF patients;
• In a negative pressure room (airborne infection isolation room);
• In a PFT laboratory with high-efficiency particulate (HEPA) filters; or
in a PFT laboratory
8.
Updated recommendations for care of nebulizers in the hospital.
9.
Only 1 person with CF may attend a CF Foundation-sponsored indoor event
Updated recommendations for IP&C in CF
I. Core Recommendations
The CF Foundation recommends implementation of the following core IP&C
recommendations to minimize the risk of transmission and acquisition of
pathogens among all people with CF, including following lung or liver
transplantation, in all settings.
Education/Adherence Monitoring for Healthcare Personnel, People with CF, and
Families
1.
All healthcare personnel caring for people with CF (eg, the CF care team,
inpatient staff, environmental services staff, research staff, and staff in diagnostic
and therapeutic areas, including pulmonary function test [PFT] laboratories,
radiology, phlebotomy, operating room, and physical therapy) receive education
regarding IP&C for CF, using principles of adult learning. Education should be
repeated at intervals each center deems appropriate.
Updated recommendations for IP&C in CF
2.
The CF care team develop strategies to monitor adherence to IP&C practices by
healthcare personnel and provide feedback. Feedback to the CF care team
includes immediate feedback to an individual when a lapse in practice is observed
and feedback to the entire CF care team of trends of overall adherence rates at
regular intervals (eg, quarterly) on the basis of consistency of practices.
3.
All people with CF and their families receive education regarding IP&C for CF,
using age appropriate tools and reading/language level appropriate to the target
audience. Involve people with CF and their families in the development of
educational programs and implementation of recommended practices. Education
should be repeated at intervals each center deems appropriate.
4.
CF care teams collaborate with their institutional IP&C teams to implement
the recommendations in this guideline.
Updated recommendations for IP&C in CF
5.
The CF Foundation recommends that CF care teams collaborate with their
institutional IP&C teams to develop protocols, checklists, and audits to
standardize implementation of practices for the following:
a. Single-patient-use, disposable items
b. Cleaning and disinfecting multiuse items (eg, patient care equipment,
oximeters, iPads and similar tablets, and computers)
c. Cleaning and disinfecting surfaces in the healthcare environment (e.g., CF
clinics, PFT rooms, hospital rooms, and sinks and showers)
6.
Ensure that dust containment during renovation and construction and waterleak
remediation policies and practices are followed according to institutional and
national guidelines in all ambulatory care areas and inpatient settings where
people with CF receive care.
Updated recommendations for IP&C in CF
7. All healthcare personnel assume that all people with CF could have pathogens
in respiratory tract secretions that are transmissible to other people with CF.
8.
All healthcare facilities caring for people with CF ensure ready availability of
alcohol-based hand rub or antimicrobial soap and water in all patient rooms, PFT
rooms, and waiting areas.
9.
All healthcare personnel perform hand hygiene (either using alcohol-based
hand rub or washing hands with antimicrobial soap and water), as per CDC and
WHO guidelines, in the following clinical situations:
a. Before entering the room and when leaving the room of any patient
b. Before and after direct contact with any patient
c. Before putting gloves on and after removing gloves, for both sterile and
non-sterile procedures
d. After contact with patient’s skin, mucous membranes, respiratory
secretions, or other body fluids
e. After contact with inanimate objects (including medical equipment) in the
vicinity of the patient that may be potentially contaminated with respiratory
secretions
Updated recommendations for IP&C in CF
10. The CF Foundation recommends that healthcare personnel should not wear
artificial fingernails or nail extenders when having direct contact with people
with CF.
There are 67 more. Do you want me to list them?
I didn’t think so!
:-)
Research Milestones
2000
Cystic Fibrosis Foundation Therapeutics (CFFT), a nonprofit research affiliate of the
Foundation, is established to govern drug discovery and development efforts.
2000
Foundation-supported scientists map the entire genetic structure of the most
common cause of CF lung infections — the Pseudomonas aeruginosa bacterium.
Researchers can identify the function of specific genes and find ways to turn off the
bad ones.
2002
A Foundation-supported study shows azithromycin improves CF lung health.
2003
Foundation-supported scientists at Structural GenomiX Inc., determine the threedimensional structure of a portion of the CFTR protein, opening the door to more drug
discovery opportunities
2004
Foundation-supported studies in Australia and at the University of North Carolina
show that hypertonic saline helps clear CF mucus. It is proven to improve lung
function and reduce hospital stays, and becomes a therapeutic option.
Research Milestones
2006
VX-770, an oral drug in development by Vertex Pharmaceuticals Inc., with support
from the Foundation, enters clinical trials. VX-770 is one of the first compounds to
attack the root cause of CF, and works at the cellular level to open chloride channels
that do not function correctly in people with the disease.
2007
Vertex selects a second potential drug, VX-809, for development. Like VX-770, VX-809
addresses the underlying cause of CF, but it works by helping the defective CF protein
move to its proper place in the cell
2008
The Foundation and Vertex achieve a “proof of concept,” showing that it is possible to
treat the root cause of CF. During Phase 2 studies of VX-770, trial participants, all of
whom carry the G551D mutation of CF, show unprecedented improvements in key
signs of the disease..
2010
The FDA approves a new inhaled antibiotic, Cayston®(aztreonam for inhalation
solution), to treat CF lung infections. Developed by Gilead Sciences Inc., Cayston offers
a much-needed antibiotic alternative for CF patients who battle recurrent infections
and develop resistance to existing antibiotics.
Research Milestones
2011
The Foundation announces that Phase 3 clinical trials of ivacaftor (formerly VX-770)
showed profound results. Those receiving the drug demonstrated the highest increase
on a lung function test seen in any clinical trial of a CF drug. Vertex submits a New
Drug Application to the FDA for ivacaftor under the trade name Kalydeco™.
2012
The FDA approves ivacaftor for people with the G551D mutation of CF ages 6 and
older. The drug is the first to address the underlying cause of CF and opens exciting
new doors to research and development that may lead to a cure for all people living
with the disease
2013
Vertex begins two large international Phase 3 trials of ivacaftor in combination with
lumacaftor (formerly VX-809) in people with two copies of the most common CF
mutation, F508del
2014
The FDA approves ivacaftor as a single therapy to treat people ages 6 and older with
one of eight additional rare CF mutations, and the drug continues to be evaluated in
more patient groups.
Research Milestones
2014
Results from Phase 3 studies of ivacaftor in combination with lumacaftor showed
significant improvement in lung function and other key measures of CF in people with
two copies of the F508del mutation of CF, ages 12 and older. Vertex plans to submit a
New Drug Application by the end of 2014 to the FDA, with possible approval in 2015
2014
The Foundation maintains a robust pipeline of potential therapies that target the
disease from every angle. The more drugs in the pipeline, the greater the odds of
producing successful therapies and a cure for CF.
20142015
Vertex plans to submit a New Drug Application (NDA) by the end of 2014 to the U.S.
Food and Drug Administration (FDA) for review, with potential approval in 2015 of the
combination treatment for people with two copies of the F508del mutation ages 12
and older.
Demonstrated stark differences in lung function as measured by FEV1% predicted between the
USA and the UK in children and young CF adults.
Differences in lung function persisted with a number of sensitivity analyses and in multivariable
adjustment for confounders. The differences were associated with very significant differences in
the aggressiveness of care, particularly in CF children, which may have long-term implications to
outcome in this disease.
Further longitudinal comparisons of national data are needed to unravel the causal implications
of earlier and more aggressive treatment of CF children.
Goss CH, et al. Thorax 2014;0:1–8.
Review content assessed as up-to-date: 23 July 2014
Background
Airway infection leads to progressive damage of the lungs in cystic
fibrosis and oxidative stress has been implicated in the etiology.
One quasi-randomized and nine randomized controlled studies were
included, with a total of 436 participants. Eight studies analyzed oral
supplementation with antioxidants and two inhaled supplements.
Supplementation of antioxidant micronutrients (vitamin E, vitamin C, ßcarotene and selenium) or glutathione may therefore potentially help
maintain an oxidant-antioxidant balance. Current literature suggests a
relationship between oxidative status and lung function.
Plain language summary
What are the effects of vitamins E and C, beta-carotene, selenium and
glutathione on lung disease in people with cystic fibrosis?
One quasi-randomized and nine randomized controlled studies were
included, with a total of 436 participants. Eight studies analyzed oral
supplementation with antioxidants and two inhaled supplements.
It’s too early to judge the effects of antioxidant supplements
Results of this review are conflicting and it’s difficult to tell which
changes are due to antioxidants and which are due to other treatments
(e.g. antibiotics)
Glutathione (either oral or inhaled) appears to improve lung function in
some cases and lower oxidative stress.
Larger studies, especially in very young patients, should look at
important clinical outcomes for at least six months before firm
conclusions regarding the effects of antioxidant supplements can be
drawn.
Quality of the evidence
None of the studies was free of possible bias. Most problems were
because data were not fully reported; this likely affected the results.
It wasn’t clear if volunteers knew in advance which group they were
going to be in and if they knew once the trials started whether they
received the supplements or placebo (blinding). This makes it unclear
how this may have affected the study results.
Challenges Ahead
The aging population of patients with CF will present clinical
challenges, including the effects of decades of taking
aminoglycoside antibiotics, microvascular complications from
CF-related diabetes, and depression and anxiety.
Comorbidities associated with aging that are more prevalent
among people with CF include colon cancer,
hypertriglyceridemia, and chronic renal insufficiency.
Challenges Ahead
"Caring for adults with CF requires a village"
"Pulmonologists, nephrologists, gastroenterologists, and other adult
specialists have not been trained to manage the complexity of diseases
such as CF“
Challenges Ahead
However, the adult medical system has had practice treating patients
with pediatric-onset diseases. "What we're seeing in CF has been a
trend across all pediatric-onset health conditions," Lisa Tuchman MD,
MPH, a specialist in adolescent medicine at Children's National Medical
Center (regarding pediatric cancers, HIV disease, and sickle cell disease)
Life expectancy for children born and diagnosed with CF in
2010 is 37 years for females and 40 years for males.