What Is Cystic Fibrosis

Cystic fibrosis (CF) is a chronic, progressive,and frequently fatal genetic (inherited) dis-ease of the bodys mucus glands. CF pri-marily affects the respiratory and digestivesystems in children and young adults. Thesweat glands and the reproductive systemare also usually involved. On the average,individuals with CF have a lifespan ofapproximately 30 years.

CF-like disease has been known for overtwo centuries. The name, cystic fibrosis ofthe pancreas, was first applied to the diseasein 1938.

How Common Is CF?

According to the data collected by theCystic Fibrosis Foundation, there are about30,000 Americans, 3,000 Canadians, and20,000 Europeans with CF. The diseaseoccurs mostly in whites whose ancestorscame from northern Europe, although itaffects all races and ethnic groups.Accordingly, it is less common in AfricanAmericans, Native Americans, and AsianAmericans. Approximately 2,500 babies areborn with CF each year in the UnitedStates. Also, about 1 in every 20Americans is an unaffected carrier of anabnormal CF gene. These 12 million people are usually unaware that they arecarriers.

F A C T S A B O U T

N A T I O N A L I N S T I T U T E S O F H E A L T HN A T I O N A L H E A R T , L U N G , A N D B L O O D I N S T I T U T E

Cystic Fibrosis

What Are the Signs and Symptomsof CF?

CF does not follow the same pattern in allpatients but affects different people in dif-ferent ways and to varying degrees.However, the basic problem is the samean abnormality in the glands, which pro-duce or secrete sweat and mucus. Sweatcools the body; mucus lubricates the respi-ratory, digestive, and reproductive systems,and prevents tissues from drying out, pro-tecting them from infection.

People with CF lose excessive amounts ofsalt when they sweat. This can upset thebalance of minerals in the blood, which maycause abnormal heart rhythms. Going intoshock is also a risk.

Mucus in CF patients is very thick andaccumulates in the intestines and lungs.The result is malnutrition, poor growth,frequent respiratory infections, breathingdifficulties, and eventually permanent lungdamage. Lung disease is the usual cause ofdeath in most patients.

CF can cause various other medical prob-lems. These include sinusitis (inflammationof the nasal sinuses, which are cavities inthe skull behind, above, and on both sidesof the nose), nasal polyps (fleshy growthsinside the nose), clubbing (rounding andenlargement of fingers and toes), pneu-mothorax (rupture of lung tissue and trap-

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2ping of air between the lung and thechest wall), hemoptysis (coughing ofblood), cor pulmonale (enlargementof the right side of the heart),abdominal pain and discomfort,gassiness (too much gas in the intes-tine), and rectal prolapse (protrusionof the rectum through the anus).Liver disease, diabetes, inflammationof the pancreas, and gallstones alsooccur in some people with CF.

When Should You SuspectThat a Child May Have CF?

CF symptoms vary from child tochild. A baby born with the CFgenes usually has symptoms duringits first year. Sometimes, however,signs of the disease may not show upuntil adolescence or even later.Infants or young children should betested for CF if they have persistentdiarrhea, bulky foul-smelling andgreasy stools, frequent wheezing orpneumonia, a chronic cough withthick mucus, salty-tasting skin, orpoor growth. CF should be suspect-ed in babies born with an intestinalblockage called meconium ileus.

How Is CF Diagnosed?

The most common test for CF iscalled the sweat test. It measures theamount of salt (sodium chloride) inthe sweat. In this test, an area of theskin (usually the forearm) is made tosweat by using a chemical calledpilocarpine and applying a mild elec-tric current. To collect the sweat, thearea is covered with a gauze pad orfilter paper and wrapped in plastic.After 30 to 40 minutes, the plastic isremoved, and the sweat collected inthe pad or paper is analyzed. Higherthan normal amounts of sodium and

A U T O S O M A L R E C E S S I V E I N H E R I T A N C E

The presence of two mutant genes (g) is needed for CF to appear. Each parent

carries one defective gene (g) and one normal gene (G). The single normal

gene is sufficient for normal function of the mucus glands, and the parents are

therefore CF-free. Each child has a 25 percent risk of inheriting two defective

genes and getting CF, a 25 percent chance of inheriting two normal genes,

and a 50 percent chance of being an unaffected carrier like the parents.

C Y S T I C F I B R O S I S G E N E

Carrier Father Carrier Mother

Normal

Gg Gg gg

Gg Gg

Carrier Carrier Affected

GG

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3chloride suggest that the person hascystic fibrosis.

The sweat test may not work well innewborns because they do not pro-duce enough sweat. In that case,another type of test, such as theimmunoreactive trypsinogen test(IRT), may be used. In the IRT test,blood drawn 2 to 3 days after birthis analyzed for a specific proteincalled trypsinogen. Positive IRTtests must be confirmed by sweatand other tests.

Also, a small percentage of peoplewith CF have normal sweat chloridelevels. They can only be diagnosedby chemical tests for the presence ofthe mutated gene. Some of theother tests that can assist in thediagnosis of CF are chest x-rays,lung function tests, and sputum(phlegm) cultures. Stool examina-tions can help identify the digestiveabnormalities that are typical of CF.

What Makes CF a GeneticDisease?

Genes are the basic units of heredity.They are located on structures with-in the cell nucleus called chromo-somes. The function of most genesis to instruct the cells to make par-ticular proteins, most of which haveimportant life-sustaining roles.

Every human being has 46 chromo-somes, 23 inherited from each par-ent. Because each of the 23 pairs ofchromosomes contains a completeset of genes, every individual hastwo sets (one from each parent) ofgenes for each function. In someindividuals, the basic buildingblocks of a gene (called base pairs)are altered (mutated). A mutation

can cause the body to make a defec-tive protein or no protein at all. Theresult is a loss of some essential bio-logical function and that leads todisease. Children may inherit alteredgenes from one or both parents.

Diseases such as CF that are causedby inherited genes are called geneticdiseases. In CF, each parent carriesone abnormal CF gene and one nor-mal CF gene but shows no evidenceof the disease because the normal CFgene dominates or recesses theabnormal CF gene. To have CF, achild must inherit two abnormalgenesone from each parent. Therecessive CF gene can occur in bothboys and girls because it is locatedon non-sex-linked chromosomescalled autosomal chromosomes. CFis therefore called an autosomalrecessive genetic disease.

The inheritance patterns for the CFgene are shown in the accompany-ing diagram. Each child, whethermale or female, has a 25 percent riskof inheriting a defective gene fromeach parent and of having CF. Achild born to two CF patients (anunlikely event) would be at a 100percent risk of developing CF.

How Is CF Treated?

Since CF is a genetic disease, theonly way to prevent or cure it wouldbe with gene therapy at an earlyage. Ideally, gene therapy couldrepair or replace the defective gene.Another option for treatment wouldbe to give a person with CF theactive form of the protein productthat is scarce or missing.

At present, neither gene therapy norany other kind of treatment exists

for the basic causes of CF, althoughseveral drug-based approaches arebeing investigated. In the mean-time, the best that doctors can do isto ease the symptoms of CF or slowthe progress of the disease so thepatients quality of life is improved.This is achieved by antibiotic thera-py combined with treatments toclear the thick mucus from thelungs. The therapy is tailored to theneeds of each patient. For patientswhose disease is very advanced, lungtransplantation may be an option.

CF was once always fatal in child-hood. Better treatment methodsdeveloped over the past 20 yearshave increased the average lifespanof CF patients to nearly 30 years.These treatment approaches aredetailed more fully below:

n Management of lung problems

A major focus of CF treatment is theobstructed breathing that causesfrequent lung infections. Physicaltherapy, exercise, and medicationsare used to reduce the mucus block-age of the lungs airways.

Chest therapy consists of bronchial,or postural, drainage, which is doneby placing the patient in a positionthat allows drainage of the mucusfrom the lungs. At the same time,the chest or back is clapped (per-cussed) and vibrated to dislodge themucus and help it move out of theairways. This process is repeatedover different parts of the chest andback to loosen the mucus in differ-ent areas of each lung. This proce-dure has to be done for children byfamily members but older patientscan learn to do it by themselves.Mechanical aids that help chest

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4HOW DOES THE GENE MUTATION

CAUSE CF?

The CF gene was identified in 1989.

Since then, a great deal has been learned

about this gene and its protein product.

The biochemical abnormality in CF

results from a mutation in a gene that

produces a protein responsible for the

movement through the cell membranes

of chloride ions (a component of sodium

chloride, or common table salt). The

protein is called CFTRcystic fibrosis

transmembrane regulator.

CFTR is present in cells that line the

passageways of the lungs, pancreas,

colon, and genitourinary tract. When

this protein is abnormal, two of the

hallmarks of CF resultblockage of the

movement of chloride ions and water in

the lung and other cells and secretion of

abnormal mucus.

The mutation involved in CF causes the

deletion of three of the base pairs in the

gene. This in turn, causes a loss in the

CFTR protein of an amino acid (the

building blocks of proteins). Because

phenylalanine is located in position 508

of the protein chain, this mutant protein

is called DF508 CFTR.

However, DF508 CFTR accounts for only

70-80 percent of all CF cases. Various

other mutationsover 400 at the last

countseem to be responsible for the

remaining CF cases. Differences in

disease patterns seen in individuals and

families probably result from the

combined effects of the particular

mutation and various, but still unknown,

factors in the CF patient and his or her

environment.

physical therapy are available com-mercially. Exercise also helps toloosen the mucus, stimulate cough-ing to clear the mucus, and improvethe patients overall physical condition.

Medications used to help breathingare often aerosolized (misted) andcan be inhaled. These medicinesinclude bronchodilators (whichwiden the breathing tubes),mucolytics (which thin the mucus),and decongestants (which reduceswelling of the membranes of thebreathing tubes). A recent advance,approved by the Food and DrugAdministration, is an inhaledaerosolized enzyme that thins themucus by digesting the cellularmaterial trapped in it. Antibiotics tofight lung infections also are usedand may be taken orally or inaerosol form, or by injection into avein.

n Management of digestive problems

The digestive problems in CF areless serious and more easily man-aged than those in the lungs. Awell-balanced, high-caloric diet,low in fat and high in protein, andpancreatic enzymes (which helpdigestion) are often prescribed.Supplements of vitamins A, D, E,and K are given to ensure goodnutrition. Enemas and mucolyticagents are used to treat intestinalobstructions.

Gene TherapyThe Future ofCF Treatment?

Gene therapy for CF is not yet pos-sible but impressive progress isbeing made in developing ways to

treat the gene abnormality thatcauses CF. In the laboratory, scien-tists have been able to grow cellsfrom the nasal passages of CFpatients. By introducing the normalgene into these cells, researcherscorrected the cells chloride trans-port abnormality. The chloridedefect has also been corrected insmall regions in the nasal passagesthemselves by giving CF patientsthe normal gene in nose drops.

Scientists are still looking foranswers to many questions aboutgene therapy. Some of these ques-tions are: How should the gene bepackaged? What are the best waysto get the gene-containing packageinto the patients lungs? What willthe long-term results of this treat-ment be? Can the abnormal chloridetransport be corrected in other partsof the body? How long will the cor-rection last? And, most importantly,can gene therapy cure or preventthe lung disease in CF?

Is It Possible to Detect CF inan Unborn Baby?

Finding out whether a baby is likelyto have CF is possible using prenatalgenetic tests. However, the testscannot detect all of the CF genemutations. Also, because these testsare very expensive and have certainrisks to the mother, they are notused for all pregnant women. Ifthere is another child with CF in thefamily, the expectant mother mayrequest a prenatal test to see if thefetus has CF genes from both par-ents, is a carrier for one gene, or isaltogether free of the CF genes.

There are two special prenatal tests

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5that can be doneeither an amnio-centesis or chorionic villus biopsywill be performed. In amniocentesis,cells from the fluid surrounding thebaby in the mothers womb (calledthe amniotic fluid) are tested to seeif the CF genes common to the par-ents are present. In chorionic villusbiopsy, cells from the tissue that willeventually form the placenta aretested for the CF gene.

Can CF Be Prevented?

At this time, preventing CF is notpossible. In babies with two abnor-mal CF genes, the disease is alreadypresent at birth in some organs,such as the pancreas and liver, butdevelops only after birth in thelungs. Someday, gene therapy maybe used to prevent the lung diseasefrom developing.

Yet, CF might be prevented in thefuture. Since CF occurs only whenboth parents pass on a CF gene to achild, it could be prevented by iden-tifying all carriers of CF genes.Genetic counselors might then per-suade couples who are carriers notto have children. However, as noted,current tests can detect only some ofthe more than 400 gene mutationsand so the tests are only 80-85 per-cent accurate.

Yet, progress in gene therapy andthe realization that not all CF muta-tions are life-threatening shouldreassure couples. Potential parentswho carry the defective gene maychoose to have children.

How Can Patients and TheirFamilies and Friends BeHelped To Cope with CF?

CF education helps patients andtheir families face the physical andemotional effects of the disease andencourages CF patients to leadactive, fulfilling lives. Educationalprograms and materials suitable forboth patients of various ages andtheir parents are available from localCF centers and from local chaptersof the CF Foundation.

Patients and their families andfriends should know that:

n CF parents should not feel guiltyor responsible for causing theirchilds disease; they could not haveprevented it.

n Parents should treat their chil-dren with CF as normally as possi-ble. They shouldnt be over-pro-tective but should encourage themto be active and self-reliant.

n Family and friends shouldremember that CF is not conta-gious; nobody can get it from apatient.

n In families with CF, brothers, sis-ters, and first cousins of the CFpatient should be tested to see ifthey carry a defective gene, especial-ly if they seem to have a chroniclung or digestive problem. Carriersof the abnormal gene should getgenetic counseling.

n Individuals with CF have normalsexual development and can expectto have a normal sex life. However,most, but not all, men are infertilebecause of a mechanical blockage ofsperm and cannot have children.Women with CF can have children,

although they may be less fertilethan women without CF.

n Patients and families shouldwork closely with doctors and othermedical specialists to develop self-management skills that can improvetheir quality of life.

Above all, CF patients and theirfamilies should keep a positive atti-tude. Scientists continue to makesignificant advances in understand-ing the genetic and physiologicaldisturbances in CF and in develop-ing new treatment approaches suchas gene therapy. The outlook isbright for further improvements inthe care of CF patients and even forthe discovery of a cure.

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6FOR MORE

INFORMATION

Additional information

about CF can be obtained

from the following

organizations:

National Heart, Lung, and

Blood Institute (NHLBI)

Information Center

P.O. Box 30105

Bethesda, MD 20824-0105

Telephone: 301-251-1222

The Cystic Fibrosis

Foundation

6931 Arlington Road, #200

Bethesda, MD 20814

Telephone: 301-951-4422

1- 800-344-4823

National Diabetes

Information Clearinghouse

1 Information Way

Bethesda, MD 20892-3560

Telephone: 301-654-3327

1-800-891-5388

U.S. DEPARTMENT OF

HEALTH AND HUMAN

SERVICES

Public Health Service

National Institutes of Health

National Heart, Lung, and

Blood Institute

NIH Publication No. 95-3650

November 1995

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