CF notes

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I. OPENING PRAYER

II. ANATOMY AND PHYSIOLOGY OF THE RESPIRATORY AND GASTROINTESTINAL TRACT

Respiratory system

The Pleurae The pleurae form a thin, double-layered serosa (see Figure 22.10). The layer called the parietal pleura covers the thoracic wall and superiorface of the diaphragm. It continues around the heart and between the lungs, forming the lateral walls of the mediastinal enclosure and snuglyenclosing the lung root. From here, the pleura extends as the layer called the visceral pleura to cover the external lung surface, dipping intoand lining its fissures.

The pleurae produce pleural fluid, which fills the slitlike pleural cavity between them. This lubricating secretion allows the lungs to glideeasily over the thorax wall during our breathing movements. Although the pleurae slide easily across each other, their separation is stronglyresisted by the surface tension of the pleural fluid. Consequently, the lungs cling tightly to the thorax wall and are forced to expand and recoilpassively as the volume of the thoracic cavity alternately increases and decreases during breathing.

The pleurae also help divide the thoracic cavity into three chambersthe central mediastinum and the two lateral pleural compartments, eachcontaining a lung. This compartmentalization helps prevent one mobile organ (for example, the lung or heart) from interfering with another. Italso limits the spread of local infections.

Gastrointestinal

From the esophagus to the anal canal, the walls of the alimentary canal have the same four basic layers, or tunics mucosa,submucosa, muscularis externa, and serosaeach containing a predominant tissue type that plays a specific role in foodbreakdown.

The Mucosa

The mucosa, or mucous membrane the innermost layeris a moist epithelial membrane that lines the alimentary canal lumenfrom mouth to anus. Its major functions are (1) secretion of mucus, digestive enzymes, and hormones, (2) absorption of the endproducts of digestion into the blood, and (3) protection against infectious disease. The mucosa in a particular region of the GI tract

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may express one or all three of these capabilities.More complex than most other mucosae in the body, the typical digestive mucosa consists of three sublayers: (1) a liningepithelium, (2) a lamina propria, and (3) a muscularis mucosae. Typically, the epithelium of the mucosa is a simple columnarepithelium rich in mucus-secreting goblet cells. The slippery mucus it produces protects certain digestive organs f rom beingdigested themselves by enzymes working within their cavities and eases food passage along the tract. In the stomach and small

intestine, the mucosa also contains both enzyme-synthesizing and hormone-secreting cells. Thus, in such sites, the mucosa is adiffuse kind of endocrine organ as well as part of the digestive organ. The lamina propria (proprius = ones own), which underlies the epithelium, is loose areolar connective tissue. Its capillaries nourishthe epithelium and absorb digested nutrients. Its isolated lymphoid follicles, part of MALT, the mucosa-associated lymphatic tissuedescribed, help defend us against bacteria and other pathogens, which have rather free access to our digestive tract. Particularlylarge collections of lymphoid follicles occur within the pharynx (as the tonsils) and in the appendix.External to the lamina propria is the muscularis mucosae, a scant layer of smooth muscle cells that produces local movements of the mucosa. For example, twitching of this muscle layer dislodges food particles that have adhered to the mucosa. In the smallintestine, it throws the mucosa into a series of small folds that immensely increase its surface area.

The Submucosa The submucosa, just external to the mucosa, is a moderately dense connective tissue containing blood and lymphatic vessels,lymphoid follicles, and nerve fibers. Its rich supply of elastic fibers enables the stomach to regain its normal shape aftertemporarily storing a large meal. Its extensive vascular network supplies surrounding tissues of the GI tract wall.

The Muscularis Externa Just deep to the submucosa is the muscularis externa, also simply called the muscularis. This layer is responsible for segmentationand peristalsis. It typically has an inner circular layer and an outer longitudinal layer of smooth muscle cells (Figure 23.6). Inseveral places along the tract, the circular layer thickens, forming sphincters that act as valves to prevent backflow and controlfood passage from one organ to the next.

The Serosa The serosa , the protective outermost layer of the intraperitoneal organs, is the visceral peritoneum. It is formed of areolarconnective tissue covered with mesothelium, a single layer of squamous epithelial cells.

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In the esophagus, which is located in the thoracic instead of the abdominopelvic cavity, the serosa is replaced by an adventitia . The adventitia is ordinary fibrous connective tissue that binds the esophagus to surrounding structures. Retroperitoneal organshave both a serosa (on the side facing the peritoneal cavity) and an adventitia (on the side abutting the dorsal body wall).

III. CLINICAL MANIFESTATION

A. RESPIRATORY TRACT

Initial pulmonary manifestations are of ten wheezing respirations and a dry, nonproductive cough. Eventually diffuse bronchialand bronchiolar obstruction leads to irregular aeration with progressive pulmonary disturbance and secondary infection. The mostprominent and constant feature of pulmonary involvement is chronic cough. Dyspnea increases, the cough often becomesparoxysmal, and the generalized obstructive hyperinflation and patchy areas of atelectasis.

Progressive pulmonary involvement with hyperaeration of functioning alveoli produces the overinflated, barrel-shaped chest inwhich the anteroposterior diameter approaches the lateral diameter. Bronchiectatic cysts and subpleural blebs in the upper lobesare observed in advanced disease; these may rupture, causing pneumothorax. When ventilation and subsequent diffusion and gasexchange are significantly impaired, cyanosis and clubbing of the fingers and toes may occur. The child or adolescent hasrepeated episodes of bronchitis and bronchopneumonia and is subject to chronic nasal congestion, rhinitis, chronic sinusitis, andnasal polyps. The incidence of ear, nose, and throat surgeries is higher in this group of children when compared with the generalpopulation.

B. GASTROINTESTINAL TRACT

The earliest postnatal manifestation of CF is meconium ileus, which occurs in 7% to 10% of newborns with the disease. Thick,puttylike, tenacious, mucilaginous meconium blocks the lumen of the small intestine usually at or near the ileocecal valve, whichgives rise to signs of intestinal obstruction, including abdominal distention, vomiting, failure to pass stools and rapid development

of dehydration with associated electrolyte imbalance. Thick intestinal secretions continue to be problematic throughout life.Children of all ages are subject to intestinal obstruction from inspissated or impacted feces. Gumlike masses in the cecum can

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obstruct the bowel, causing pain, nausea and vomiting. This is referred to as meconium ileus equivalent. Distal intestinalobstruction syndrome is the name given to a partial or complete intestinal obstruction that occurs in some children with CF.

C. REPRODUCTIVE SYSTEM

Delayed puberty in girls with CF is common even when their nutritional and clinical s tatus is good. The reproductive systems

of both male and females with CF are affected. Females with CF have normal fallopian tubes and ovaries. Fertility can be inhibitedby highly viscous cervical secretions, which act as a plug, blocking sperm entry. Women with CF who become pregnant have anincreased incidence of premature labor and delivery and low birth weight in the infant. Most adult men (95%) with CF are sterile,which may be caused by blockage of the vas deferens with abdominal secretions or by failure of normal development of thewolfian duct structures (vas deferens, epididymis, and seminal vesicles), resulting in decreased or absent sperm production.

D. INTEGUMENTARY

The consistent finding of abnormally high sodium and chloride concentrations in the sweat is a unique characteristic of CF.Parents frequently observe that their infants taste salty when they kiss them. The chloride channel defect in sweat glandsprevents reabsorption of sodium and chloride, which leaves the affected person at risk for abnormal salt loss, dehydration, and

hypochloremic and hyponatremic alkalosis during hyperthermic conditions. This is especially important to the infant because of limited fluid stores and the potential for inadequate sodium intake with most commercially prepared infant formulas.

IV. COMPLICATIONS

A. BRONCHLECTASIS

Frequent complications of cystic fibrosis a re chronic respiratory infections, including pneumonia, bronchitis, chronic sinusitis andbronchiectasis an abnormal dilation of the walls of the bronchial tubes that makes it more difficult to clear your airways. Asthmacan result from chronic inflammation of the bronchial lining.

B. PNEUMOTHORAX

People with cystic fibrosis may also develop bleeding from the lungs (hemoptysis), respiratory fa ilure or collapsed lung(pneumothorax) a condition in which lung a ir leaks into the chest cavity through a small hole that forms in the lung's outer

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layer. Lung disease eventually may cause the lower right chamber (right ventricle) of the heart to fail. Ultimately, complicationsfrom lung problems may prove fatal for many people with cystic fibrosis.

C. RESPIRATORY TRACT INFECTION

Respiratory infections are common because thick mucus blocks the airways and provides an ideal breeding ground for bacteria. The most common infective agent in people with cystic fibrosis is Pseudomonas aeruginosa a bacterium that can causeincreased inflammation of the respiratory tract. Although antibiotics can decrease the frequency and severity of attacks , thebacteria are never completely eradicated from the airways and the lungs. On the other hand, P. aeruginosa rarely causespulmonary infections in healthy people and isn't considered contagious.

D. NUTRITIONAL COMPLICATION

In addition, cystic fibrosis makes you prone to chronic diarrhea and severe nutritional deficiencies. That's because thick secretionsobstruct the ducts in your pancreas, preventing enzymes that digest fats and proteins from reaching your intestines. Thesesecretions also prevent your body from absorbing the fat-soluble vitamins A, D, E and K.

Cystic fibrosis affects the pancreas and because the pancreas controls the level of sugar in your blood, up to one in five peoplewith cystic fibrosis may develop cystic fibrosis-related diabetes. In addition, the bile duct, the duct that carries bile from your liverand gallbladder to your small intestine, may become blocked and inflamed, leading to liver problems such as cirrhosis.

V. MEDICAL MANAGEMENT

A. DIAGNOSTIC

Sweat test: Several methods are used to conduct a sweat test. Performed properly, the quantitative pilocarpine iontophoresis test(QPIT) to collect sweat and perform a chemical analysis of its chloride content is currently considered to be the only adequatelysensitive and specific type of sweat test.

Sweat testing involves application of a medication that stimulates sweating (pilocarpine) to one electrode of an apparatus and

running electric current to a separate electrode on the skin. This process, called iontophoresis, causes sweating; the sweat is thencollected on filter paper or in a capillary tube and analyzed for abnormal amounts of sodium and chloride. People with CF have

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increased amounts of sodium and chloride in their sweat. CF can also be diagnosed by identification of mutations in the CFTRgene.

During the procedure, a small amount of an odorless sweat-producing chemical is applied to a small area on the arm or leg. An

electrode attached to the area stimulates a very weak and painless electric current, causing a tingling or warm feeling. Afterseveral minutes, sweat is collected from the stimulated area and sent to a laboratory for analysis.

The sweat test is performed on two separate samples, which are usually taken on one occasion, to ensure that a false-positive orfalse-negative result hasn't occurred. A consistently high level of salt indicates cystic fibrosis. This test doesn't show whethersomeone has a mild or severe case of the disease, however, and it can't predict how well someone with cystic fibrosis will do.

In addition, the sweat test may not always be useful in newborns. That's because babies may not produce enough sweat for areliable diagnosis in the first month of life. For this reason, doctors usually don't perform a sweat test until an infant is at leastseveral months old.

For reliable results, collect at least 50 mg or, preferably, 100 mg of sweat. Current macroduct collection methods allow adequateanalysis with smaller volumes of sweat. The sweat chloride reference value is less than 40 mEq/L, and a value of more than 60mEq/L of chloride in the sweat is consistent with a diagnosis of CF. The sweat test must be performed at least twice in eachpatient, preferably several weeks apart. Values of 40-60 mEq/L are considered borderline, and the test must be repeated becausethese values have been found to be consistent with the diagnosis in some patients with typical features.

Repeat a sweat test to confirm positive results. Repeat a sweat test with negative results if clinical features suggestive of CF arepresent. Some patients with genetically documented CF and typical symptoms have consistently negative results on sweat tests.

Other causes of elevated levels of sweat chloride include the following:

Hypothyroidism

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Vasopressin-resistant diabetes insipidus

Malnutrition

Iatrogenic causes (ie, infusion of prostaglandin E1, improper technique)

Imaging Studies:

Chest radiography: Initial changes are hyperinflation and peribronchial thickening. Progressive airtrapping with bronchiectasis maybe apparent in the upper lobes. With advancing pulmonary disease, pulmonary nodules resulting from abscesses, infiltrates withor without lobar atelectasis, marked hyperinflation with flattened domes of the diaphragm, thoracic kyphosis, and bowing of thesternum develop. Pulmonary artery dilatation and right ventricular hypertrophy associated with cor pulmonale is usually maskedby marked hyperinflation. Several radiologic scoring systems exist.

Sinus radiography: Panopacification of the sinuses is present in almost all patients with CF, and its presence is strongly suggestiveof the diagnosis. Conversely, absence of panopacification strongly suggests that CF is not present.

Other Tests:

Genotyping

More than 1300 CF mutations have been identified. In the commercially available CF gene sequencing method, the entire codingregion, splice junction sites, and promoter region of the CFTR gene are amplified from genomic DNA by polymerase chain reaction(PCR) and the subjected to nucleotide sequence analysis on an automated capillary DNA sequencer. This test can detect morethan 98% of disease-causing mutations. The detection rate is lower in African American, Hispanic, and Asian populations;therefore, failure to find 2 abnormal genes does not exclude the disease.

A finding of 2 CFTR mutations in association with clinical symptoms is diagnostic, but negative results on genotype analysis do not

exclude the diagnosis.

Semen analysis: Obstructive azoospermia, in the absence of any other obvious cause (eg, vasectomy), provides additional

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corroborative evidence for the diagnosis of CF. Confirm results from semen analysis by obtaining a testicular biopsy.

Nasal potential difference measurement

Potential difference (PD) (voltage) measured from nasal mucosa and the reading obtained by a reference electrode inserted intothe forearm correlates with the movement of sodium across cell membranes, which is a physiologic function rendered abnormal

by a CFTR mutation. The nasal potential difference (NPD) is a sensitive test of electrolyte transport that can be used to support orrefute a diagnosis of CF. A normal mean value standard error (SE) is 0.9-24.7 mV; an abnormal value is 1.8-53 mV. Whenmeasurements are repeated after mucosal perfusion with amiloride to block an epithelial sodium channel, the drop in PD isgreater in patients with CF (73%) than in control subjects (53%). Normally, subsequent perfusion with chloride-free solution andisoproterenol produces a sharp increase in the PD but has little effect when CFTR function is abnormal.

As a result of the lack of commercially available equipment and the practical difficulties with NPD measurement, this test isperformed in only a few research centers to diagnose CF in patients in whom making a diagnosis is difficult or a sweat test is nottechnically possible because of skin problems.

Procedures:

Pulmonary function testing (PFT)

Standard spirometry may not be reliable until patients are aged 5-6 years; however, some younger patients can be taught to doreproducible maneuvers. Partial flow-volume curves may show abnormalities, in addition to an elevated airway resistance, andhyperinflation.

The recently described forced oscillation technique (FOT), which uses the impulse oscillometry system (IOS), can be usedsuccessfully in younger children. Airway resistance measured by IOS has been found to be similar to the airway resistancemeasured by body plethysmography, and this technique has been successfully used to measure lung function in young patientswith CF unable to perform spirometry.

Typically, peripheral airway involvement resulting from CF manifests as an obstructive defect with airtrapping and hyperinflation;oxyhemoglobin desaturation may occur because of a ventilation-perfusion mismatch. In the early stages, forced expiratory volumein 1 second (FEV 1 ) may be normal and forced expiratory flow (FEF) after 25-75% of vital capacity has been expelled (FEF 25-75) is

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reduced, suggesting small airway involvement. As the disease progresses, FEV 1 is also reduced.

The associated airtrapping results in an elevated ratio of residual volume to total lung capacity (RV/TLC). With hyperinflation, TLCis also increased. In patients with advanced disease, extensive lung changes with fibrosis a re reflected as restrictive changescharacterized by declining TLC and vital capacity.

Bronchoalveolar lavage: Airway inflammation is the hallmark of CF lung disease. Studies suggest airway inflammation even in theabsence of infection. Bronchoalveolar lavage fluid usually shows a high percentage of neutrophils, and recovery of Pseudomonasaeruginosa from bronchoalveolar lavage fluid supports the diagnosis of CF in a clinically atypical case.

Sputum microbiology: The most common bacterial pathogens in the sputum of patients with CF are Haemophilus influenzae,Staphylococcus aureus, P aeruginosa, Burkholderia cepacia, Escherichia coli, and Klebsiella pneumoniae . Findings of P aeruginosa, especially the mucoid form, support the diagnosis of CF in children.

Cystic fibrosis may be diagnosed by newborn screening, sweat testing, or genetic testing. As of 2006 in the United States, tenpercent of cases are diagnosed shortly after birth as part of newborn screening programs. The newborn screen identifiesdecreased amounts of the enzyme trypsin. However, most states and countries do not screen for CF routinely at birth. Therefore,most individuals are diagnosed after symptoms prompt an evaluation for cystic fibrosis. The most commonly used form of testingis the sweat test

A multitude of tests is used to identify complications of CF and to monitor disease progression. X-rays and CAT scans are used toexamine the lungs for signs of damage or infection. Examination of the sputum under a microscope is used to identify whichbacteria are causing infection so that effective antibiotics can be given. Pulmonary function tests measure how well the lungs arefunctioning, and are used to measure the need for and response to antibiotic therapy. Blood tests can identify liver problems,vitamin deficiencies, and the onset of diabetes. DEXA scans can screen for osteoporosis and testing for fecal elastase can helpdiagnose insufficient digestive enzymes.

Both the gene test and the sweat test are accurate in diagnosing CF. However, neither can accurately predict how severe thechilds symptoms will be.

This is the diagnostic criteria for Cystic Fibrosis

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Presence of typical clinical features (respiratory, gastrointestinal, or genitourinary) OR

A history of CF in a sibling OR

A positive newborn screening test PLUS

Laboratory evidence for CFTR dysfunction:

Two elevated sweat chloride concentrations obtained on separate days OR

Identification of two CF mutations OR

Abnormal nasal potential difference measurement

B. PHARMACOLOGICAL

The primary goals of cystic fibrosis (CF) treatment include maintaining lung function as near to normal as possible by controllingrespiratory infection, clearing airways of mucous, administering nutritional therapy (ie, enzyme supplements, multivitamin andmineral supplements) to maintain adequate growth, and managing complications.

Medications intended for cystic fibrosis patients include:

Antibiotics. Newer antibiotics may more effectively fight the bacteria that cause lung infections in people with cystic fibrosis.Among these are aerosolized antibiotics that send medication directly into airways. One of the major drawbacks of long-term use

of antibiotics is the development of bacteria that are resistant to drug therapy.Antibiotic treatment may vary from a short course of one antibiotic agent to a continuous course with multiple antibioticsadministered via various routes, including PO, IV, or inhalation. Since patients with CF have a larger lean body mass, they often

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have a higher clearance rate for many antibiotics. Achieving effective levels in respiratory secretions is difficult; higher doses of antibiotics and monitoring of aminoglycoside levels are required.

Administer aerosolized antibiotics when the airway pathogens are resistant to oral antibiotics or when the infection is difficult tocontrol at home. Aerosolized antibiotics may reduce symptoms by reducing the organism density in the airways. Other advantagesinclude prevention of infection or delay of chronic colonization, treatment of acute infection, and treatment of bacterial

colonization in patients following transplantation to prevent infection in the transplanted lungs.Of all the agents used in the aerosolized form (eg, gentamicin, colistin, tobramycin), preservative-free high-dose tobramycin isespecially formulated for inhalation (ie, TOBI) and has been used in 2 la rge controlled studies and been reported to be safe andeffective in patients older than 6 months. Usual dose is 300 mg bid given during alternate months. Currently clinical trials using apowder form of tobramycin and colistin are underway. These preparations will use novel delivery devices and result in shorteningthe time required for dosage administration.

Cephalosporins are effective against staphylococci and H influenzae . A small subset of third-generation cephalosporins is effectiveagainst P aeruginosa . Generally speaking, moving from first-generation to third-generation cephalosporins gives increasing gram-negative coverage and less gram-positive coverage.

Fluoroquinolones are effective against most gram-positive and gram-negative organisms. They are the only class of oral antibioticseffective against P aeruginosa . The most commonly used medication in this class is ciprofloxacin. None are approved for childrenbecause of concern regarding their effects on deposition in the cartilage. However, studies from Europe have reported substantialevidence of their safety in patients with CF.

In patients with colonization with P aeruginosa , azithromycin administered PO 3 times/wk on a long-term basis has been shown toimprove lung function, nutritional status, and reduce acute pulmonary exacerbations.

Drug Name Tobramycin, inhaled (TOBI) -- Formulated specifically for inhalation.Chronic intermittent administration in patients with P aeruginosa infectionimproves pulmonary function and nutritional status and reduces

Contraindicati Documented hypersensitivity

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Interactions Concurrent use with systemic aminoglycosides has caused ototoxicity

Precautions May cause bronchospasm, voice alterations, or tinnitus

Drug Name Gentamicin (Garamycin) -- Usually combined with one of the penicillinsused to treat pseudomonad infections in patients with CF.


Interactions

Coadministration with other aminoglycosides, cephalosporins, penicillins,and amphotericin B may increase nephrotoxicity; because aminoglycosidesenhance effects of neuromuscular blocking agents, prolonged respiratorydepression may occur; coadministration with loop diuretics may increaseauditory toxicity of aminoglycosides; possible irreversible hearing loss of

PrecautionsRenal toxicity and ototoxicity are possible adverse effects; drug-levelmonitoring is required to ensure therapeutic levels and minimize adverseeffects; high-frequency hearing loss and tinnitus may occur; adjust dose in

Drug NameCloxacillin (Cloxapen, Tegopen) -- For treatment of infections caused bypenicillinase-producing staphylococci. May be used to initiate therapywhen a staphylococcal infection is suspected.


Interactions Decreases efficacy of oral contraceptives; may decrease effects of anticoagulants; probenecid and disulfiram may increase penicillin levels

Precautions Monitor PT in patients taking anticoagulant medications; toxicity mayincrease in patients with renal impairment

Drug Name

Cephalexin (Keflex, Biocef, Keftab) -- First-generation cephalosporin that

arrests bacterial growth by inhibiting bacterial cell wall synthesis.Bactericidal activity against rapidly growing organisms. Primary activity

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Interactions Coadministration with aminoglycosides increases nephrotoxic potential

PrecautionsAdverse effects may include rash, thrombophlebitis, nausea, vomiting, anddiarrhea; approximately one third of patients who are allergic to penicillinare sensitive to cephalosporins; adjust dose in severe renal insufficiency(high doses may cause CNS toxicity); superinfections and promotion of

Drug NameCeftazidime (Ceptaz, Fortaz, Tazidime, Tazicef) -- Third-generationcephalosporin with broad-spectrum gram-negative activity; lower efficacyagainst gram-positive organisms; higher efficacy against resistantorganisms. Arrests bacterial growth by binding to one or more penicillin-


Interactions Nephrotoxicity may increase with aminoglycosides, furosemide, andethacrynic acid; probenecid may increase levels

PrecautionsAdverse effects may include rash, thrombophlebitis, nausea, vomiting, anddiarrhea; approximately one third of patients who are allergic to penicillinare sensitive to cephalosporins; adjust dose in severe renal insufficiency(hi h doses ma cause CNS toxicit ); su erinfections and romotion of

Drug NameCiprofloxacin (Cipro) -- Fluoroquinolone with activity against Pseudomonasorganisms, streptococci, MRSA, Staphylococcus epidermidis, and mostgram-negative organisms but with no activity against anaerobes. Inhibitsbacterial DNA s nthesis and, conse uentl , rowth. Oral bioavailabilit is


Interactions

Antacids, iron salts, and zinc salts may reduce serum levels; administerantacids 2-4 h before or after taking fluoroquinolones; cimetidine mayinterfere with metabolism of fluoroquinolones; ciprofloxacin reducestherapeutic effects of phenytoin; probenecid may increase ciprofloxacinserum concentrations; may increase toxicity of theophylline, caffeine,

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PrecautionsDue to possible deposition in growing cartilage, use is not routinelypreferred in children, and if used, preferred use is for short periods;perform periodic evaluations of organ system functions (eg, renal, hepatic,hematopoietic) during prolonged therapy; adjust dose in renal function

Drug Name Trimethoprim and sulfamethoxazole (Bactrim, Septra) -- The broadspectrum and action of trimethoprim (TMP) and sulfamethoxazole (SMZ)against organisms found in patients with CF and the convenience of PO

Contraindicati Documented hypersensitivity, megaloblastic anemia due to folate

Interactions

May increase PT when used with warfarin (perform coagulation tests andadjust dose accordingly); coadministration with dapsone may increaseblood levels of both drugs; coadministration of diuretics increasesprevalence of thrombocytopenia purpura in elderly persons; phenytoinlevels may increase with coadministration; may potentiate effects of methotrexate in bone marrow de ression; h o l cemic res onse to

Precautions

Contraindicated in pregnancy near term; discontinue at first appearance of skin rash or sign of adverse reaction; obtain CBCs frequently; discontinue if

significant hematologic changes occur; goiter, diuresis, and hypoglycemiamay occur with sulfonamides; prolonged IV infusions or high doses maycause bone marrow depression (if signs occur, administer 5-15 mg/dleucovorin); caution in folate deficiency (eg, chronic a lcoholism or patientswho are elderly, receiving anticonvulsant therapy, or have malabsorptionsyndrome); hemolysis may occur in patients with G-6-PD deficiency;

-

Drug NameChloramphenicol (Chloromycetin) -- Effective against H influenzae andstaphylococcal species. May help treat P aeruginosa infection for unclearreasons. Oral preparation no longer available in the United States.


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Interactions

Administered concurrently with barbiturates, serum levels may decreasewhile barbiturate levels may increase, causing toxicity; manifestations of hypoglycemia may occur with sulfonylureas; rifampin may reduce serumlevels, presumably through hepatic enzyme induction; may increase

Precautions

Contraindicated in pregnancy near term because of potential toxic effects

on fetus (gray syndrome); can cause dose-related bone marrowsuppression or idiosyncratic reaction, causing more serious aplasticanemia; patient should have hemoglobin, hematocrit, and white blood cellcount at frequent intervals during therapyUse only for indicated infections or as prophylaxis for bacterial infections;serious and fatal blood dyscrasias (aplastic anemia, hypoplastic anemia,thrombocytopenia, granulocytopenia) can occur; evaluate baseline and

erform eriodic blood studies a roximatel ever 2 d while in thera

Mucus-thinning drugs. When your white blood cells attack bacteria in your airways, DNA in the cells is released, making themucus in your airways even thicker. The aerosolized drug dornase alfa (Pulmozyme) is an enzyme that fragments DNA, making

mucus thinner and easier to cough up. Side effects of the drug may include airway irritation and sore throat.

Large amounts of neutrophil-derived DNA released from the dead neutrophils increase sputum viscosity. Mucolytics, such asdornase alfa, an enzyme that hydrolyses the DNA, are used in patients with CF to improve airway clearance.

A recent comparative trial of patients receiving 7% hypertonic NaCl (4 mL via nebulizer bid) versus patients receiving normalsaline in similar fashion, were shown to have improved lung function and fewer pulmonary exacerbations. At this time, 7%hypertonic saline is not commercially available.

Drug NameDornase alfa (Pulmozyme) -- Recombinant human DNase (rhDNase).Cleaves and depolymerizes extracellular DNA and separates DNA fromproteins. This allows endogenous proteolytic enzymes to break down the

Contraindicat Documented hypersensitivity

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Interactions None reported

Precautions May cause hoarseness, pharyngitis, rash, or chest pain

Bronchodilators. Use of medications such as albuterol (Proventil, Ventolin) may help keep open the bronchial tubes by clearing

thick secretions.

Albuterol provides selective agonistic action on beta2-adrenoceptors. Stimulate adenyl cyclase resulting in smooth musclerelaxation of the bronchi, uterus, and skeletal muscle. Inhaled beta2-agonists are often administered before chest physical therapyfor airway clearance. They also are indicated when clinical evidence of bronchial hyperresponsiveness exists. In children with CF,use of bronchodilators must be evaluated. Children with bronchiectasis may have a paradoxic bronchodilatation in response tobeta-adrenergic agents. Pulmonary function testing before and after bronchodilators is suggested to avoid thesecounterproductive effects.

Drug Name

Albuterol (Proventil, Ventolin) -- Most commonly used bronchodilatingagent available in multiple dosage forms (eg, solution for nebulization,metered-dose inhaler, oral solution). Typically, 2.5 mg of albuterolnebulizer solution is used either in premix solution with isotonic sodium


InteractionsBeta-adrenergic blockers antagonize effects; inhaled ipratropium mayincrease duration of bronchodilatation by albuterol; cardiovascular effectsmay increase with MAOIs, inhaled anesthetics, tricyclic antidepressants,

PrecautionsBeta2-agonists may decrease PaO2 by increasing ventilation-perfusionmismatch and decreasing airway wall tone, resulting in enhanced airwaycollapse during expiration; caution with conditions associated with

Pain relievers. Ibuprofen (Advil, Motrin) may slow lung deterioration in some children with cystic fibrosis.

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Enzymes, pancreatic -- These agents aid digestion when the pancreas is malfunctioning. Current pancreatic enzymepreparations are derived from porcine extracts and contain various proportions of lipase, amylase, and protease. Most of thepreparations are available in multiple strengths. A particular dose is prescribed based on clinical symptoms and age and weightand then modified according to the clinical response. Usually, the dose of pancreatic enzymes should not exceed 2000 U/kg/mealof lipase. The novel preparation TheraCLEC-Total, a highly purified microbiologically-derived enzyme preparation, is underinvestigation in clinical trials.

Drug NamePancrelipase (Cotazym, Creon, Ultrase, Viokase, Zymase) -- Enteric-coatedpancreatic enzyme microspheres containing various amounts of lipase,

rotease, and am lase. Assists in di estion of rotein, starch, and fat.Contraindicati Documented hypersensitivity, history of pork protein allergy

Interactions Drugs that increase gastric pH (eg, H2 antagonists, proton pump inhibitors)may increase effect of pancreatic enzymes by inhibiting destruction of

Precautions

Monitor weight gain or loss, abdominal cramps, frequency and nature of stools, and bloating; patient can take more enzymes with large fattymeals; caps should be swallowed whole or sprinkled on food immediatelyprior to ingestion and should not be chewed, crushed, or taken with hotliquids; coadministration with H2 blockers or proton pump inhibitors toreduce gastric acid production (ie, optimizes pH [5-6.5] for enzymedissolution) helps reduce daily dose of pancreatic enzymes; intake of hi her dose of ancreatic enz mes (more than recommended dose) has

Vitamins -- Vitamins are organic substances required by the body in small amounts for various metabolic processes. They may besynthesized in small or insufficient amounts in the body or not synthesized at all, thus requiring supplementation. They areclassified as fat or water soluble. Vitamins A, D, E, and K are fat soluble while biotin, folic acid, niacin, pantothenic acid, B vitamins

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(ie, B-1, B-2, B-6, B-12), and v itamin C are generally water so luble.

Vitamin deficiency may result from an inadequate diet, increased requirements (eg, pregnancy, lactation), or secondary to diseaseor drug use. They are used clinically for the prevention and treatment of specific vitamin deficiency states. Supplementation of fat-soluble vitamins is routine in CF because of chronic malabsorption.

Drug Name

Vitamins, fat soluble -- Vitamins A, D, E, and K are fat-soluble vitamins andare essential for antioxidant effects and function as coenzymes forbiological pathways, neurodevelopment, bone development, andcoagulation. Typical multivitamin preparations formulated especially forpatients with CF are referred to as ADEKs. The following doses are typicallyare rescribed for diseases of malabsor tion.

Contraindicat Documented hypersensitivity, pregnancy (ie, vitamin A and D doses

InteractionsVitamin K counteracts effects of oral anticoagulants; prolonged use of phenytoin or phenobarbital may exacerbate vitamin D deficiency; bile acid

binding resins (eg, cholestyramine) may decrease absorption of fat-solublevitamins; large doses of vitamin E may prolong PT, requiring dose

Precautions

Pregnancy category X (ie, vitamin A, vitamin D) if doses exceed RDAVitamin A may cause irritability, drowsiness, vertigo, headache, increasedintracranial pressure, erythema, and cheilosis with doses exceedingphysiologic replacementVitamin D may cause hypercalcemiaVitamin E may induce vitamin K deficiency; necrotizing enterocolitis mayoccur with large doses of vitamin E

C. SURGERIES

Surgical therapy may be required for the treatment of respiratory complications such as pneumothorax, massive recurrent or

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persistent hemoptysis, nasal polyps, or persistent and chronic sinusitis. Gastrointestinal tract complications, such as meconiumileus, intussusception, gastrostomy tube placement for supplemental feeding, and rectal prolapse, also require surgical therapy.Lung transplant is indicated for the treatment of end-stage lung disease.

The physician may suggest lung transplantation if you have severe breathing problems, life-threatening pulmonary complicationsor increasing resistance to antibiotics used to treat lung infections. Whether you're a good candidate for the procedure depends ona number of factors, including your overall health, certain lifestyle factors and the availability of donor organs. Because both lungsare affected by cystic fibrosis, both need to be replaced. If your chest isn't large enough to hold two adult donor lungs, yoursurgeon is likely to use two lower lobes contributed by two living donors. However it's performed, lung transplantation is a majoroperation and may lead to serious complications, especially post-surgical infections.

VI. NURSING MANAGEMENT

A. ASSESSMENT

The symptoms and severity of CF vary from person to person. Some people with CF have serious lung and digestive problems.Other people have more mild disease that doesn't show up until they are adolescents or young adults.

For example, one child with cystic fibrosis may have respiratory problems but not digestive problems, while another child mayhave both. In addition, the signs and symptoms of cystic fibrosis may vary with age.

Signs and symptoms in newbornsIn some newborns the first sign may be a blockage of their intestines (meconium ileus). This occurs when meconium tarry,greenish-black stools normally passed by an infant in the first day or two after birth becomes so thick it can't move through theintestines. Other signs in newborns may include:

Failure to grow

Bulky and greasy stools (steatorrhea) Frequent respiratory infections

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Signs and symptoms in children and young adults The signs and symptoms of cystic fibrosis in children and young adults may include:

Salty taste to the skin. People with cystic fibrosis tend to have higher than normal amounts of salt (sodium chloride) in theirsweat. This may be one of the first signs parents notice because they taste the salt when they kiss their child.

Blockage in the bowels. Foul-smelling, greasy stools.

Delayed growth. Thick sputum. It's easy for parents to overlook this sign because young children tend to swallow their sputum rather than

cough it up. Coughing or wheezing. Frequent chest and sinus infections with recurring pneumonia or bronchitis. Protrusion of part of the rectum through the anus (rectal prolapse). This is often caused by stools that are difficult to pass or

by frequent coughing. Enlargement or rounding (clubbing) of the fingertips and toes. Although clubbing eventually occurs in most people with

cystic fibrosis, it also occurs in some people born with heart disease and other types of lung problems.

Cystic fibrosis also may be accompanied by: Growths (polyps) in the nasal passages Cirrhosis of the liver due to inflammation or obstruction of the bile ducts Displacement of one part of the intestine into another part of the intestine (intussusception) in children older than age 4

Some infants and children with CF gain weight and grow normally, but many grow more slowly than unaffected children. This isbecause sticky mucus blocks pancreatic enzymes from reaching the small intestine, where most digestion and absorption of nutrients takes place. As a result, af fected children may absorb fewer calories and nutrients, leading to slow growth.

Many individuals with CF experience symptoms related to poor digestion. These include:

Slow weight gain, in spite of a good appetite Frequent, loose or large bowel movements Bowel movements that contain mucus or oil Gas, stomach pain and bloating

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The symptoms of CF vary and can range from mild to severe. Some common symptoms include:

Coughing or wheezing Repeated lung infections, such as pneumonia and bronchitis Shortness of breath Poor growth, in spite of a big appetite Intestinal blockage, called meconium ileus, in a newborn (caused by thickening of the greenish stool newborns usually pass

in the first days of life) Greasy, bulky stools Infertility in affected males due to blockage or absence of the tube (vas deferens) that carries sperm out of the testicles

Respiratory failure is the most common cause of death in people with CF.

B. INDEPENDENT MEASURES

Nursing care for the client with cystic fibrosis is much the same as for any chronic obstructive lung disease. The geneticcomponent of the disease and the clients age are important considerations. Adults with CF are just entering their productive yearsand face a lifespan that is likely to be shortened significantly. Females who do conceive face the prospect of transmitting the

defective gene to their offspring.

The following nursing diagnosis are all appropriate for the client with CF:

Ineffective Airway Clearance

Ineffective Breathing Pattern

Anxiety

Imbalanced Nutrition: Less Than Body Requirements

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Compromised Family Coping

Education of the client and family affected by cystic fibrosis is essential to maintaining optimal health. Young adult patients,teaching is significant since they do not yet established a lot of knowledge. The health teaching should include:

Respiratory care techniques including percussion, postural drainage, and controlled cough techniques

Specific breathing and coughing exercises and procedures

The importance of avoiding respiratory irritants

Measures to prevent respiratory infection, such as maintaining immunizations and optimal general health and avoiding exposureto large crowds and infected people

As a health care provider it is best to:

Provide counseling at the time of initial diagnosis, including information regarding inheritance and risk for recurrence insubsequent pregnancies.

Instruct patients and parents regarding appropriate airway clearance technique and the need for chest physical therapy.

Instruct patients and parents regarding the use of various drug delivery devices, such as spacers and nebulizers.

Instruct patients and parents regarding methods for modifying the pancreatic enzyme dosage.

Discuss when to contact CF center personnel (eg, for acute pulmonary exacerbation or complications) with patients and parents.

Be prepared to counsel families regarding the impact of the diagnosis on the emotional life of parents, siblings, and members of

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the extended family.

Moreover, it is best to teach the patient and the family regarding self care:

If there a child with cystic fibrosis, one of the best things to do is to learn as much as possible about the disease. Diet, medication

and early recognition of infection are important.Also important for most patients is performing daily chest percussion to drain mucus from the child's lungs. The physician orrespiratory therapist as well as the nurse can show the best way to perform this lifesaving procedure.

In addition, the following steps can help aid the child's health:

Keep child's immunizations up-to-date. This includes child's pneumococcal and influenza vaccines. Cystic fibrosis doesn'taffect the immune system, but children with cystic fibrosis are more likely to develop complications when they become sick.

Encourage the child to lead as normal and active a life as possible. Exercise is extremely important for people of all ageswho have cystic fibrosis. Regular exercise helps loosen mucus in airways and strengthens heart and lungs. And for many peoplewith cystic fibrosis, participating in sports can improve confidence and self-esteem. It isn't necessary to take part in an organizedsport or take classes a t a gym. Anything that gets the person moving, including walking and biking, can help.

Make sure the child eats a healthy diet. Be sure to discuss child's dietary needs with a doctor or a nutritionist. Use nutrition supplements. Provide the fat-soluble vitamin supplements and pancreatic enzymes the child needs to stay ashealthy as possible.

Emphasize liquids. Encourage child to drink plenty of liquids to help loosen the mucus. This is especially important in thesummer when children are active and tend to lose a lot of fluids.

Eliminate smoke. Don't smoke in home or car, and don't allow other people to smoke around the child. Secondhand smoke isharmful for everyone, but especially for people with cystic fibrosis.

Encourage hand washing. Teach everyone in the family to wash their hands thoroughly before eating, after using the bathroom,when coming home from work or school, and after being around a person who is sick. Hand washing is the best way to protect

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against infection.EVALUATION

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