2. INTRODUCTION
is a multisystem disease affecting the digestive system,
sweat glands, and the reproductive tract, but progressive
lung disease continues to be the major cause of morbidity
and mortality. Patients with CF have abnormal transport
of chloride and sodium across the respiratory epithelium,
resulting in thickened, viscous airway secretions
3. GENETICS
CF is caused by mutations in a single large gene on
chromosome 7 that encodes the cystic fibrosis
transmembrane conductance regulator (CFTR)
protein . Clinical disease requires disease-causing
mutations in both copies of the CFTR gene.
4.
5.
6. PATHOGENESIS
CFTR malfunction is associated with low water content in
secretions from the respiratory, pancreatic, and biliary
epithelium, which causes the secretions to be viscous and
difficult to clear.
GIT: the abnormal bile and pancreatic secretions cause
maldigestion and malabsorption, progressive liver and
pancreatic disease, rectal prolapse, and intestinal
obstruction (distal intestinal obstruction syndrome or
intussusception).
7. CONT.
Lung: the abnormal secretions cause chronic airway
obstruction and reduce bacteriocidal killing, leading to
progressive pulmonary colonization with pathogenic
bacteria, and to the formation of bacterial biofilms. Chronic
infection causes an inflammatory response and tissue
destruction, causing bronchiectasis. Infection with P.
aeruginosa is particularly favored in patients with CF, due to
abnormally decreased oxygen tension within the
hyperviscous mucous layer.
8. EPIDEMIOLOGY
CF occurs in approximately 1:3000 Caucasians, 1:9200
Hispanics, 1:10,900 Native Americans, 1:15,000 African
Americans and 1:30,000 Asian Americans .
16. CFTR MODULATORS (Ivacaftor )
is a small molecular weight oral drug that is
specifically designed to treat patients who have a
G551D mutation in at least one of their CFTR genes.
We recommend ivacaftor for all CF patients 6 years of
age and older who carry at least one copy of the
G551D CFTR mutation. Ivacaftor, 150 mg PO every 12
hours, should be taken with fat-containing foods.
17. ANTIBIOTICS
Chronic treatment with oral antibiotics is not
encouraged because the benefits have not outweighed
the problems associated with antibiotic resistance
with 2 exceptions:
Azithromycin : its benefits may be due to its
antiinflammatory and/or antibacterial properties.
Nebulized antibiotics directed against Pseudomonas
aeruginosa (eg, tobramycin and aztreonam) appears
to improve lung function and is recommended for
many patients.
18. BRONCHODILATORS
There is clinical evidence that chronic use of beta-2-
adrenergic receptor agonist therapy increases
expiratory flow rates in patients with CF . This has led
to the recommendation that clinicians
prescribe albuterol every four to six hours, or a long-
acting beta-agonist (salmeterol or formoterol) every
12 hours .
19.
AGENTS TO PROMOTE AIRWAY SECRETION
CLEARANCE
Inhaled DNase I (dornase alfa) : decrease the viscosity of
purulent CF sputum by cleaving long strands of denatured
DNA that are released by degenerating neutrophils.
Inhaled hypertonic saline :hydrate inspissated mucus
that is present in the airways of patients with CF.
CHEST PHYSIOTHERAPY
21. Cont.
inhaled glucocorticoids: Although it seems reasonable to
continue prescribing aerosolized glucocorticoids to CF
patients who have definite signs and symptoms of asthma or
ABPA there is insufficient evidence to warrant broader use.
We agree with the guidelines committee of the CF
Foundation, which recommends against their routine use .
