Diagnosis and Treatment of Cystic Fibrosis

[ i today’s ti -practice Diagnosis

of cardioPuImonar

and Treatment

of Cystic

medicine

Fibrosis*

An Update Pamela B. Davis, M.D. Paul A. di Sant’Agnese,

,

Ph.D. M.D.

,

; and Med. Sc.Dr

fibrosis

is the most common fatal inherited disease of At present, cystic fibrosis accounts for most cases of chronic progressive pulmonary disease and for many other clinical features in the first three decades of life. Thus, it is a challenge to both pediatricians and internists, particularly chest physicians. The diagnosis is based on the triad of chronic obstructive pulmonary disease, pancreatic insufficiency, and increased levels of electrolytes in the sweat. The cardinal test for confirmation of the diagnosis is the “sweat test,” which is an excellent discriminant for cystic fibrosis, even in adults. Ancillary features of cystic fibrosis Cystic

Caucasians.

may

be ofdiagnostic

Treatment Choice sputum

pathogen.

O

assistance

(eg, nasal

polyposis,

Pseudo-

in sputum, azoospermia, and others). of the pulmonary disease must be emphasized. of antibiotics should be based on the results of culture, but P aeruginosa is the most common

aeruginosa

monas

Removal

stic

fibrosis

of

secretions

is the

most

by

regular

common

fatal

in

Orientals. transmitted

native African The consensus

as

Despite

intensive

chemical

error

a simple

blacks is that

autosomal

research, remains

an

the

inherited

and full-blooded cystic fibrosis

recessive

is bio-

enigma.

Cystic fibrosis was only recognized as a separate disease in 1938. Despite this short history, the clinical syndrome is well described. The classical clinical triad of chronic obstructive pulmonary disease (COPD), pancreatic

deficiency,

electrolytes

in the

other suria,

diverse intestinal

and sweat

manifestations, obstruction,

may

abnormally

high

be accompanied

such as cirrhosis, and azoospermia,

levels

of

by many

glycoto make

*Fmm the Pulmonary Division, Department ofMedicine, Veterans Administration Medical Center, Cleveland, and the Pediatric Metabolism Branch, National Institute of Arthritis, Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, Md. Reprint requests: D Davis, Pulmonary Division, VA Medical Center, Cleveland 44106

802

massive

ofthe

is an integral

part

hemoptysis,

cor pulmonale,

program.

and may be encountered. Sinusitis is almost universal, and nasal polyposis is frequently present. Pancreatic insufficiency occurs in over 80 percent of the patients with cystic fibrosis and may result in intestinal malabsorption. Massive salt loss through the sweat in hot weather, a distinctive type of biliary cirrhosis without jaundice, gallbladder abnormalities, choleithiasis, and diabetes mellitus also may be found. Of special importance are intestinal obstructive complications (meconium ileus in newborn infants with cystic fibrosis and intestinal obstruction due to fecal accumulation or intussusception in adults). Azoospermia is present in 95 percent ofmen and there is reduced fertiuity in women; however, pregnancy does occur in cystic

other complications

fibrosis.

This

chronic

and

fatal

ultimately

set of psychosocial

disease

produces

first

cystic

in its prognosis

fibrosis,

dramatic

a

complications.

a truly protean clinical picture. In the 40 years following the changes

descriptions

of have

taken place. Median survival has increased tenlbld, to more than 20 years today (Fig 1), and the quality of life has improved immensely through better understanding of the clinical nosis, and better survival,

trait.

underlying

percussion

and

Pneumothorax,

predictable

postural

disease of Caucasians, occurring in about one in 2,000 live births. About 5 percent ofthe white population carries the gene. In American blacks, the mcidence of cystic fibrosis is about one in 17,000 and the carrier rate about 2 percent. The disease is much less common

drainage

more

early and accurate diagcare. With increasing

syndrome, supportive

patients

with

this complicated,

ultimately fatal illness will challenge and internists, particularly chest coming

and

years.

This report emphasizes of cystic fibrosis.

treatment

chronic,

both pediatricians physicians, in the the

diagnosis

DIAGNOSIS

Cystic chronic

fibrosis pulmonary

life, for most and

accounts

cases

maldigestion

pancreatic

insufficiency

fibrosis adults

and

of progressive

intestinal

decades

of

malabsorption

in children, and for nearly all of the and intestinal obstruction due

nasal

should be who present Diagnosis

cases

in the first three

of severe

to meconium ileus fibrosis is implicated prolapse,

for most

disease

in the newborn. in many cases polyps. suspected with these

and 1 eatment

The

In addition, ofcirrhosis, diagnosis

in children complaints Cystic

Fibrosis (Davis,

cystic rectal of cystic

or young as well as a L

Sant’Agnese)

20

Other indications Sibling with cystic Nasal polyposis Azoospermia Infertility (women) Heat prostration

>

w C!, -J

Metabolic

> >

10

The stration

cr

:D U)

nary

5

cystic 1960

1970

CALENDAR FIGuan 1. Median after 1968 are taken

survival

for

patients

1980

cystic

fibrosis.

Data

from Data Registry of Cystic Fibrosis Foundalion. Data prior to 1968 are taken from estimates published in thencurrent literature. Improvement in survival occurred until 1975, after which median survival has not significantly increased.

wide

vaijety

of others,

including

recurrent

heat

pros-

tration, intestinal obstruction, infertility, or pancreatitis. Pulmonary disease in cystic fibrosis may present explosively with staphylococcal pneumonia or insidiously with persistent cough following upper respiratory

infection.

respiratory

infections,

Recurrent a

roentgenogram,

chronic

tasis,

of

recovery

cystic the

mucoid

fibrosis.

asterisk regardless that cystic symptom, unless patients

The

Pseudomonas or “asthma”

following

for sweat

indicates

cough,

that

sweat

testing

is

in the

cause first

Pulmonary Mucoid “Asthma” Recurrent

is

three

established, decades

fibrosis

intact

values

may

conditions,

(eg,

untreated

less

occur

exocrine

results

(an

.

.

of

sweat

separates

1 to 2 percent and about one

than

50 mEq/L

more

frequently

pancreatic

function.

occur

in patients

clinically adrenal

(Fig

in pa“False-

with

edema.

from

distinct insufficiency,

cystic ectoder-

CHILDREN

.

(N-1094)

40. 30.

for

mandatory

especially

0 w 10’ U) U-

0 ADULTS-PULMONARY

for

DISEASE (N=1 87)

20

of life):

indications P aeruginosa in sputum5 or COPD with deteriorating lower respiratory infectionst

have

values

a few

aeruginosa an abnor-

of other manifestations; a dagger indicates fibrosis is an extremely common cause of the and sweat testing should not be omitted

another

Only fibrosis

in the

than 60 mEq/L, 50 and 60 mEq/L,

lower

with

history

tan’2

chest

summarizes

for cystic

greater between

negative”

A family

cystic fibrosis from those without the without overlap (Fig 2). Over 98 percent with cystic fibrosis have a sweat chloride

or fewer

2). ’ The tients

or both.

pulmoexocrine

bronchiec-

with

tabulation

testing

in 1,000

setting of chronic character or

concentration

with disease almost ofthe patients concentration have values

is made by demonof chloride (and

lower

or progressive deterioration should prompt investigation

function

indications

abnormal

productive

from the respiratory tree, mal chest roentgenogram in pulmonary

or prolonged

persistent

chloride

mucus

(unexplained)

is of diagnostic

children

YEAR with

insufficiency

fibrosis

The

1950

in infancy

alkalosis

in the sweat in the disease of appropriate

pancreatic

w

with thick cervical

diagnosis of cystic fibrosis of an elevated concentration

sodium)

z

fibrosis5

a-

courset

CF

(N=213)

Bronchiectasist

cough

Chronic Lobar

atelectasis

Staphylococcal Gastrointestinal

pneumonia

(infants)

indications

Meconium iieus5 Pancreatic insulliciencyt Rectal prolapset Meconium ileus equivalentt in young adultst cirrhosis (without jaundice) Pancreatitis in pediatric age group Choleithiasis in children Intussuseeption J3iliary

20

40

60

80

100 120

140

SWEAT CHLORIDE CONCENTRATION Cm Eq/I) Ficuan 2. Distribution of sweat chloride concentrations in 1,094 children without cystic fibrosis (top panel), 355 healthy normal adults (second panel), 187 adults with pulmonary disease (third panel), and 213 patients with cystic fibrosis (CF) (bottom panel). Histograms were redrawn from published data(see references 4 and 6 for sources). Even in adult age range, sweat chloride level is an excellent discriminant for cystic fibrosis. CHEST

I 85 I 6 I JUNE,

1984

803

mal

dysplasia,

elevated

or renal

sweat

diabetes

sodium

and

insipidus),

chloride

concentrations values for sweat

(“false-positive” tests).5 The normal sodium and chloride concentrations with age, discriminant

but

however, laboratories

the “sweat test” for cystic fibrosis

performance or failure

increase

method

unacceptable

percentage a very

excellent (Fig 2);

j FLAMMAT

or

ofGibson

and Cooke

oferror

and

leads

to an

misclassification

tive, with aeruginosa

sweat

chloride

concentration

infection (often

fibrosis is strong absence of family occasional cases, such as azoospermia the

confirm

diagnosis;

with

with

sinuses,

fibrosis when

criterion8

\

CNDl:1PL

may of the

is usually proper sex.

ofthe diagnostic azoospermia as a cases.

Even

in

bronchiectasis

infection

lar obstruction Inflammation bronchial Destruction 804

(Fig 3). Bronchiolitis

flow

tory

occur

and

unusual

early;

patchy

collapse

(Fig

rates,

5). This

maximal expiratory

leads

in cystic

fibrosis,

although

to

midexpiravolume in

capacity sense

it increases

is with

advancing age, but diffuse obstruction with hyperinflation is prominent at necropsy and is manifested in life by an increase in the residual residual volume to total lung pulmonary

disease

at combatting

ofsecretions. pulmonary

of of

nowadays

is

pathophysiology

of

infection treatment

and promoting

and is

removal

fibrosis is a disease of smoldering and inflammation with periodic Exacerbations may be triggered by viral and measles and influenza are especially

infections,

so immunization

devastating,

crucial.

Other

given

on schedule. for patients

Exacerbations efibrts

fibrosis

to chronic with mucus,

infection

course

The

Cystic infection

exacerbations.

sary

in cystic

is attributable the airways

and the ratio

volume capacity.

in years or even decades. much ofthe pulmonary

Because

aimed

inft ction spread throughout the tree, with plugging or larger airways. of tissue in the walls of airways leads to

results

one second, and, later, a reduced forced vital as well. ‘frue emphysema in an anatomic

fibrosis plugging of

and bronchioatelectasis follows.

and progression

physiology

with decreased a reduced forced

airflow

cystic

bacterial

4). Obstructive

expiratory

impaired

picture.

lungs are morphologically normal at birth, but months, or decades later, infection initiates a cycle ofinflammation, mucous hypersecretion, of clearance of mucus, and failure to eliminate

mechanisms ofdevelopment in cystic fibrosis (CF).

(Fig

permitting

measured

Disease

CCR PtUVPSLE

plugging ofthe airways with thick mucus, inflammation and edema ofthe airways, bronchoconstriction, and loss of the supporting structure of the airways,

the

failure

Y\\

from

immotile cilia syndrome, immunoglobulmn defiand other similar disorders, and either secretin test7 or at least fecal fat studies, will usually clarify the

TREATMENT

A

DEATH

ciency,

vicious

(a =ICTICN

I

Ficuwn 3. Postulated ofpulmonary disease

the

The weeks,

WLL ’

NDUECTA5!S

patients, the “sweat test” is an excellent discrimifor cystic fibrosis6 (Fig 2); this test, in conjunction careful pulmonary evaluation, with exclusion of

Pulmonary

CouissV

to Secystic

others,4

90 percent

for most

E 51PA1tRYJ

\

P

enzyme

response confirmed

and semen in those ofthe

proposed revision fibrosis including

i)

I YPERIPI’I TIoN

by elevated intact

and over

is not helpful

\

suppura-

are made in patients less the sweat test is very nearly

discriminant, for analysis even

Thus, the recently criteria for cystic major

CLaM hsacnci

be

aureus or Gram-negative

or indirectly

however,

15 years

an absolute unavailable

FAILIO

evidence for the diagnosis, but an history is not helpful. if needed in ancillary features of cystic fibrosis, in men, roentgenographic abnor-

of cystic ofage,

diagnoses

must

OBSTRUCTION

CLEmNa

must

obstructive physiolmay be documented

patients

paranasal

of the

malities

nant

with

drainage even

both

is usually

have impaired bicarbonate A sibling or first cousin with

release cretin.7

older

disease

progressive, insufficiency

excretion;

fat

or

by Staphylococcus mucoid) or other

by duodenal

feed

than

insufficiency

pulmonary

organisms, and gy”2 Pancreatic directly

1I

1BR0 CHIAL

high

pancreatic

The

present.

I

oiocc siaicrica

occur in the appropriate clinical setting to establish the diagnosis of cystic fibrosis. Either chronic pulmonary disease

I

LCFUI!

patients.5 Even

frz’or

INFECTION

slightly

is still an in adults6

H,tabOUO

of this test in inexperienced to use the standard pilocarpine

iontophoresis of

la.io

produce

to remove

childhood

against

these

immunizations

Pneumococcal vaccine with cystic fibrosis. are

managed

respiratory

viruses

should

is not neces-

with intensification secretions and antibiotics

D agno&s and Weatment of Cystic Fibtosis (Devis

is

also be

L Sant’Agnes.)

of

‘V

4

p Ficuax

L

4. Chest

bronchiectatic and B (right),

roentgenograms ofa 33-year-old woman with cystic fibrosis, illustrating extensive changes, loss ofvolume in left upperlobe, and hyperinilation. A (left), Posteroanterior lateral view

selected recovered

on the basis of the sensitivities of organisms in the sputum. if the exacerbation is mild

and appropriate tient treatment more serious nisms,

oral antibiotics are available, outpawith oral agents may be attempted. For exacerbations or more resistant orga-

parenteral

antibiotics

Since P aeruginosa the antibiotics selected such

blood

are

is the are

most often

indicated. frequent pathogen, an aminoglycoside

and a semisynthetic

as tobramycin

as ticarcillin. patients with the

cysticview;

are usually

penicillin

such

of these drugs required to achieve a given level

The dosages cystic fibrosis

higher

than

those

by in

required

by

“normal” acutely ill adults.9”#{176}To obtain in the blood and to avoid toxic effects,

adequate levels monitoring of

peak

ofthese

and

serum

trough

concentrations

drugs,

especially aminoglycosides, is mandatory. More resistant strains ofP aeruginosa as well as multiply-resistant strains of P cepacia or maltophilia may demand treatment

newer

with third-generation agents (eg, ceftazidine).

for treatment it is difficult therapy; weeks,

Ficuan 5. Lung ing consolidation, sive

lions.

bronchiectasis,

23-year-old man with cystic fibrosis, illustrathemorrhagic pneumonitis in upper lobe, exten-

from

and

filling

ofairways

with

mucopurulent

secre-

ofexacerbations to

determine

cephalosporins Since proper are not well the

optimal

or other end points established, duration

of

treatment is usually continued for at least two but considerably longer periods may be re-

quired for patients whose who have had frequent past. Controlled bmnchiectasis,

studies

condition responds exacerbations in

in patients

or chronic

bronchitis

with

slowly or the recent

cystic show

CHEST/85/6/JUNE,1984

fibrosis,

that contin805

uous

antibiotic

bations

therapy

in patients

reduces

who

the

have

number

frequent

of exacer-

relapses,11

not that the rate of decline of pulmonary function is slowed or life prolonged. Patients who have frequent and

exacerbations

those

whose

condition

if antibiotics are withdrawn should chronic, suppressive (not prophylactic) apy.

Asymptomatic

with

patients

function should tions. Outpatient

and

the

reach the most antipseudomonas found

to

trial;’4

that

in

do

a double-blind

however,

therapy

aerosols

long-term

was

when

Hg,

be

with

used

needed. It is noteworthy

that

postural

the

emphasis

are different, an obstructive pattern

ofthe

Complications Management

Pulmonary

of

the

disease

many

of cystic

aids to bringing

up sputum

as

but bland

aerosols

appear to confer no benefit. The benefits of mucolytic agents have not been demonstrated in vivo. Airway reactivity is frequent in patients with cystic fibrosis, and bronchodilator drugs are often consid-

ered;

however, deterioration

served,

disappointing of pulmonary

so patients

monitored

using

for untoward

airway

reactivity calcium channel not been studied

asthma

have the

in acute fibrosis.

should

Drugs

which

exacerbations Patients with

bronchopulmonary

indications

patient’s

bronchodilators effects.’9’m

or allergic

specific

paradoxic been ob-

without causing brbnchodilation blockers or cromolyn sodium) in cystic fibrosis.

The use of steroids been studied in cystic tant

results or even function have

for steroid

inflammatory

be

response

Although occurs

with

ated

cystic

it is rare in childhood, as 20 percent of the

with

a signfficant

are probably occurs

Hein#{243}ptysi&

about 8 percent and treatment

for

at the

present

streaking

ofthe

and

hemoptysis

carries

expected from Rarely’, hemoptysis

or

drowning

no excess

severity of the disease is so massive that exfollows rapidly. liouble-

some, recurrent massive hemoptysis has been treated by resection ofthe bleedinglobe (ifthe site of bleeding

identified

by arteriographic

the

delivery,

cor 806

pulmonary

and can

pulmonale.

disease

besides produce

pulmonary

To avoid

hypoxia

progresses,

compromising such

tissue hypertension

complications,

su-

oxygen and every

ofthe

undeilying

diuretics

special

hazard,

digoxin.

pulmonary

supplemental approaches.

sation,

Pulmonary

may has

a resection)’ if it can be

studles.u

persists, therapeutic

As

mortality

the

progress may provide such therapy.

about

sputum

ofthe adults.3 Usually, supportive of the underlying infoction are

Cor Ptilnwnak. The hypoxia of severe pulmonary disease produces pulmonary sion, which in turn leads to cor pulmonale.

information

agents

dihydroTherefore, abrasion)

time.

can be located and the patient can tolerate or by embolization of the bleeding vessel

may

all

(Atabrine available. or pleural

Blood

that

sanguination

to infection

of failure

half of the older patients, but massive (more than 500 ml in 24 hours) occurs in

hemoptysis only care

rate

always at is associ-

in over

effective,

however,

bilat-

but almost of the pleura

hydrochloride is not readily (pleurectomy

preferable

Massive

beyond itself. ’

has not co#{241}comi-

if it is symptomatic,

to pulmonary injury, and suppression of the inflammatory response may be beneficial. A prospectiv#{233} randomized controlled study of long-term alternate-day therapy with steroids in cystic fibrosis now in

pervenes,

the

treat-

in as many

fibrosis.3

except quinacrine chloride), which surgical approaches

(#{233}g, have

contribute

important

with

eral, or more than 15 percent, tube thoracostomy is indicated. The rate of recurrence is high, about 50 percent, so more definitive intervention may be con-

alter

aspergillosis therapy;

of

begins

pneumothorax

treatments

are controversial,

although they of pulmonary

drainage

sidered even at the first episode, the second. Chemical sclerosis

Aerosol

of

ment of the underlying chronic pulmonary disease, but often, specific therapies are needed in addition.

anti-

or both have been suggested to produce results.’7’ The benefits to patients who little sputum are unknown, and long-term assessed.

control

complications

fibrosis

cal exercise equivalent

not been

if

Disease

adults

have

on

60

is different from the usual chronic bronchitis/emphydrugs are first-line ther-

is an integral part of most programs to treat cystic fibrosis and improves airflow immediately in patients producing more than 30 to 50 ml of sputum per day.1#{176} Directed coughing sessions or regular physi-

benefits

above at home

similarly

and percussion

produce

Po2

therapy

apy, and the role of infection in the progression of disease is uncertain. The physiopathology, bacteriology, and natural history of cystic fibrosis and chronic

Pneumothorax. by regular

the

oxygen

infection in cystic fibrosis therapeutic emphasis in sema, where bronchodilator

pulmonary

‘

of secretions

to maintain

supplemental

function. ’

not

placeboaerosol

ineffective

mm

bronchitis/emphysema have in common

regions of the lung, chronic delivered by this route was

beneficial

staphylococcal

evaluated. Removal

pulmonary

organisms are antibioare sometimes used.’4 of selecting resistant

probability

diseased therapy

be

controlled

normal

on ther-

not be treated except during exacerbatreatment with culture-specific anti-

biotics is difficult ifthe patient’s tic-resistant; aerosol antibiotics Despite the theoretical risk organisms

deteriorates

be maintained antibiotic

should

eflbrt

but

disease

and,

oxygen therapy For frank cardiac be been

helpful. shown

vasodilators

obstruE tive hypertenTreatment

No

if hypoxemia are

the

benefit,

from

main

decompen-

but

therapy

are

under

Abiosis

(DeWs,

active

no with

in-

vestigation. Diagnosis

and Treatment

of Cystic

1 Sanf’Agnese)

Hypertrophic bing

Pulmonary

is almost

in cystic

fibrosis

no treatment, but hypertrophic thropathy, characterized by pain, ing

over

the

distal

and periosteal

in older

occasionally

usually monary

responds disease

Syndrome

bones

with

patients

and may

osteoarswell-

of cimetidine is a promising, adjunct to therapy.v Vitamin

synovitis

be disabling.3

has

ofpulmonary

pul-

reported

and

cystic

in

fibrosis

is no exception.3 Water restriction and treatment of the underlying infection are the mainstays of therapy. Sinusitis and NasalPolyposi& system is not spared in cystic

The upper fibrosis.

graphic

paranasal

sinuses

are

cystic

fibrosis.

For

abnormalities

nearly

universal

of in

bacterial sinusitis, often accomplished

the

adults

with

antibiotic during

therapy treatment

disease.

Nasal

polyps

occur

children

and

nearly frequently

half

fibrosis,3

are

regress steroids,

is appropriate but ofthe pulmonary

normal

in

cystic

may be morphologically but it is rarely, if ever, fibrosis.

Reduction

occurs in nearly all patients,7 and secretion ofdigestive enzymes is impaired pancreatic

ducts

are plugged

rial; in the late stages, replace the parenchyma Langerhans,

fibrosis

of

with

endocrine

may

cause

abdominal

well

Other

controlled

the

picture with the

and,

mate-

insufficiency with cystic flatulence,

amenable Sweat

dium

permeability metabolic

prostration hydration

in any and salt

lelithiasis) intestinal more ciency, tions.4’ ciency

cho-

and abnormal feed stream (contributing to obstruction). Pulmonary function declines slowly

in

and they

patients have

lower

without sweat

For all of these reasons, should be treated and

pancreatic chloride pancreatic the best

insufficoncentrainsuffipossible

nutrition achieved by patients with cystic fibrosis. Pancreatic enzyme supplements are administered in sufficient dosage to control symptoms and reduce steatorrhea. Enteric coated microsphere preparations of pancreatic enzymes (Pancrease; Cotazyme 5) are

resultare

The

in

reduction

must

30 minutes),

for cardiovascular

with

is common

with

fibrosis,

portal patients.3

may with

collapse

follow

but

the

extensive

hypertension,

first

be achieved

no reported

cirrhosis,

occurs

Jaundice

failure extremely uncommon. treatment for cirrhosis; however, shunting,

and (10 ml!

form of focal biliary circoncretions in the bile ducts,

eosinophilic

of the

immediate

be undertaken

to hyperthermia may surprising rapidity.

in cystic

frequently percent

develops,

A distinctive

CirrhosLs

rhosis,

in passive

Maintenance of adequate is the best preventive mea-

prostration

due with

fibrosis

the sweat duct and may in infants and to heat

replacement

first

are of so-

cystic

fluid

and death symptoms

also

which

concentration

sweat

a specific

patient. intake

may

of

therapy.

high

along alkalosis

organs

some

the

the

of the patient for many of

If heat

Gallbladder mon in cystic

to

of other

in

from

to result

chloride lead to

circulation

(predisposing

the or

dominates

the fate accounts

or specific

chloride

appears

sure.

disease

symptoms,

Abnormality.

and

hepatic

bile

occurs, by ketosis

Symptoms hyperglycemia

of

pulmonary

to prevention

of malabsorption of

insufficiency complicated

involvement

quences

entero-

supplements

by insulin.

troublesome

hemorrhage

abnormal

nutritional

and determines pancreatic lesion,

symptoms,

cause

diarrhea, and rectal prolapse. Also, the fatty acid composition ofbody lipids is altered, and deficiency of some fat-soluble vitamins may occur. Secondary conseinclude

lipid

prescribed; in water-

Complications

clinical

the

of inactiva-

by administration

but still experimental, supplements in double

vascular complications. the osmotic effects

kg in the the The

as exocrine

pam,

Specific studied.

vigorous

may entirely the islets of

as well

function. Frank pancreatic in over 80 percent of the patients and

at

in most, as well.

eosinophilic

advancing fibrosis and compromise

impairing

normal functionally

of bicarbonate

output

occurs

cystic fail to

Disease

The pancreas birth and beyond,

pancreatic

of the

adults with and, if they

form. being

Although

or with nasal insufflation repeated resections.

spontaneously may require

Pancreatic

respiratory Roentgeno-

in 10 to 15 percent

of the recurrent,

miscible

usually

acid

daily allowance are be administered separately

are now

secondary ing from

Prevention

by gastric

if endocrine pancreatic resulting diabetes is rarely

Hormone

been

diseases,

It

underlying agents.

enzymes

the recommended vitamin E must

occurs

Antidiuretic

complication

patients.

tion ofthese

and

adjacent

by most

requires

on the roentgenogram,

of Inappropriate

types

and

pulmonary warmth,

to treatment of the and anti-inflammatory

This

Secretion. many

long

elevation

well-tolerated

Club-

Osteoai-thropathy.

universal

is rare There is prevention

by early

in 2 to 5

and

hepatic

no specific of vanceal

portal-systemic

instances

of encephalopa-

thy. Abnormalitie& Microgalibladder, fibrosis, requires no treatment.

stones are common as well, tic circulation of bile acids

and abnormal

ciency

appears

and

due

malabsorption

their pathogenesis.u Regular atic enzyme supplements lithogenic. Intestinal to 15 percent

cornGall-

enterohepato pancreatic insaffito

administration may make

Obstruction. Meconium of the newborns with

contribute

to

of pancrethe bile less

ileus occurs cystic fibrosis

in 10 and,

in uncomplicated cases, can often be managed by meglumine diatrizoate (Hypaque Meglumine; Gastro-

grafin)

enemas.

Failure

ofthis CHEST

conservative I 85 I 6 I JUNE,

therapy 1984

or

807

complications

demand

surgical

and

intervention.

In older patients, intestinal obstruction is also common, occuring in up to 20 percent of the adults.3 It results

from fecal accumulation,

junction, should

because be liquid,

mal foces lead

densely

meglumine

adherent

manifestations

diatrizoate;

possible.3

Since

recurrent,3

surgery

is

measures,

such

sis develop libido,

normal and

secondary

ever, the mesonephric are usually maldeveloped consequent

sexual

if

(Colace) by obstruction cystic

fibro-

characteristics,

performance;

occurs

in over

95 percent

of

Women

with

secondary

sexual

genital have

cystic

tracts

fibrosis

develop

and

libido,

characteristics

are

structurally fertility, largely

reduced

also

normal and

their

intact; however, they because the cervical

mucus is thick and forms a mechanical barrier to sperm penetration. This problem has been circumvented by artificial insemination, placing the sperm beyond the however, women with cystic fibrosis who do pregnant face some risks. In one series of 129 pregnancies, there was a 13 percent incidence of

weight incidence percent

of ft tal wastage, chance ofthe child

chances

for

pulmonary

successful disease

and having

pregnancy is mild.

are

methods of contraception appear to be both effective is monitored. Psychosocial Complicatior&& timately fatal disease produces complications

vary

bility cystic

of psychosocial fibrosis center

as an

important

neglected

obtained

support program of

total

should not be from professionals

and set

care,

one

of availa-

not

to

be

normal physiology. and discussed, and

delayed and experienced

should be in chronic

illness. Despite fibrosis often until shortly the marriages, 808

these

complications,

have excellent before death.3 on the whole,

patients

with

cystic

success in work or school Many patients marry, and are successful.3

A hopeful

fibrosis

is

potassium

secretion

except

for the

(chronic

patient,

from

childhood,

cirrhosis,

The

the consemay arise

birth

before

or adolescence. chloride,

is present

and,

to connect

although

to a

birth

from

difficult

and to the

some

com-

that patients with essentially normal

cystic lives,

exist.

realized and lead

secondary

pulmonary

pulmonary

complications.

sodium,

must

obstruct

hepatic

abnormality,

denominator

Thick,

and

organs reflect complications

and has been

life

clinical

changes disease,

due

to the

pancreatic

disease

deficiency,

etc). Therefore, despite the fact that all of the treatments for cystic fibrosis are palliative and not curative, it is eminently worthwhile for the patient and for the physician to embark on a vigorous and optimistic designed as possible. that

achieve specific

to preserve Some ofthe

goal

treatment

have must

normal strategies

been await

function for now in use

as to

outlined herein. More more specific biochemi-

cal knowledge ofthe pathophysiology and of the disease process.

ofthe

basic

error

REFERENCES

1 di Sant’Agnese

ulof

manifestations

Routine

of sweat

extent,

mucous mon

in infancy,

the

is a regular part of a and is cited by patients

urgency to restore should be anticipated

Difficulties consultation

facet

the

individuals.

in the

when

is not desired,

This chronic a predictable

,

among

greatly

2.5 The

or oral contracepand safe if the patient

tives

psychosocial

best

Ifpregnancy

barrier

which

the expected cystic fibrosis.

cystic

most of the understood.

other

in the life ofthe

later

throughout

long

incidence of an II percent

in

rise to chronic

and

elevation

lesser

regimen

a 41 percent 4.5 kg (10 lb),

is

precipitate

changes in these of this lesion. These

to much

become

heart failure, gain of less than

physician

instifficiency,

obstruction,

pathologic quences

cervix;

congestive

ofthe

of well

giving

It is not sufficiently fibrosis would do well

the men.3

part

defect

secretions

organ passages, thus disease, pancreatic

The how-

basic pathogenesis is relatively

mucous

at any point with

derivatives (vas deferens, etc) or absent, and azoospermia

infertility

the the

intestinal

as administra-

sexual

normal

Although

tenacious

be avoided is frequently

to

dioctyl sodium sulfosuccinate are often undertaken; however,

normal

as

of2O percent

obstruction

recur despite these precautions. Reproductive Complication& Men

with

serving

is enemas

intestinal

preventive

tion of mouth, can

unknown,

to the bowelwall

on the

CONCLUSIONS

at the ileocecal

usually

treatment

attitude

appropriate.

the feed stream is semisolid where it or from intussusception, with abnor-

Primary

point.

supportive

therefore

PA, Davis PB. Research in cystic fibrosis. N Engl I Med 1976; 295:481-85, 534-41, 597-602 2 Wood RE, BoatTF, DoershukCF. Cystiefibrosis. Am Bev Bespir Dis 1976; 113:833-78 3 di Sant’Agnese PA, Davis PB. Cystic fibrosis in adults: 75 cases and a review of 232 cases in the literature. Am J Med 1979; 66:121-32 4 Davis PB, Hubbard VS, di Sant’Agnese PA. Low sweat electrolytes in a patient with cystic fibrosis. Am J Med 1980; 69:643-49

5 Report ofthe committee for a study for evaluation oftesting for cystic fibrosis. J Pediatr 1976; 88:711-34 6 Davis PB, Del Rio S. Muntz JA, Dieckman L. Sweat chloride concentration in adults with pulmonary diseases. Am Rev Respfr Dis

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PR, Corey M, Wei P. Forstner CC. Evidence for a primary defect of pancreatic HC03 secretion in cystic fibrosis. Pediatr Bes 1982; 16:554-57 8 Stern RC, Boat iT, Doershuk CE Obstructive azoospermia as a diagnosliccriterionforthecysticfibrosis syndrome. Lancet 1982; 7 Gaskin

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D agno s

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Rabin HR. Evaluation of high dose tobramycin and ticarcillin treatment protocol in cystic fibrosis. In: Sturgess JM, ed. Perspectives in cystic fibrosis. Mississauga, Ontario: Imperial Press, 1980:370-82 11 Loening-BaucheVA, MischlerE, MyersG. Aplacebo-controlled 10

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NS, Vosti KL, Dowling HF, Lepper MH, Jackson cc. Long term treatment of bronchiectasis and chronic bronchitis. Arch Intern Med 1959; 103:345-53 Hodson ME, Penketh ARL, BattenJC. Aerosolcarbenicillin and gentamicin treatment of Pseudomonas aeruginosa in patients with CF Lancet 1981; 2:1137-39 Nolan C, Mclvor P, Levison H, Fleming PC, Corey M, Gold R. Antibiotic prophylaxis in cystic fibrosis: inhaled cephaloridine as an adjunct to oral cloxacillin. J Pediatr 1982; 101:626-30 Murray JR The ketchup-bottle method. N Engl J Med 1979; 300:1155-57 Bossman CM, Waldes R, Sampson D, Newhouse MT Effect of chest physiotherapy on the removal of mucus in patients with cystic fibrosis. Am Rev Respir Dis 1982; 126:131-35 Zach M, Oberwaidner B, Hausler F Cystic fibrosis: physical exercise versus chest physiotherapy. Arch Dis Child 1982; 57:557-89 Shapiro CC, Bamman J, Danarek P. Bierman CW. The paradoxical effect of adrenergic and methyixanthine drugs in cystic fibrosis. Pediatrics 1976; 58:740-43

Larsen CL, Barren RJ, Cotton EK, Brooks JG. A comparative studyofinhaled atropine sulfate and isoproterenol hydrochloride in cystic fibrosis. Am Rev Respir Dis 1979; 119:399-407 21 Boat TF, Petty U. Chronic bronchitis and cystic fibrosis: two chronic obstructive lung diseases ofadults. Am Rev Respir Dis 1977; 116:1-2 22 Stowe SM, Boat TF Mendelson H, Stern RC, Tucker AS, Doershuk CF Open thoracotomy for pneumothorax in cystic fibrosis. Am Rev Respir Dis 1975; 111:611-17

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Stern RC, Wood RE, Boat iT, Mathews LW, Tucker Doershuk CF ‘freatment and prognosis ofmassive hemoptysis cystic fibrosis. Am Rev Respir Dis 1978; 117:825-28

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Caskin K, Gurwitz D, Dune P. Corey M, Levison H, ForstnerG. Improved respiratory prognosis in patients with cystic fibrosis with normal fat absorption. J Pediatr 1982; 100:857-62

Hubbard VS, Dunn GD, Lester LA. Effectiveness of cimetidine as an adjunct to supplemental pancreatic enzymes in patients with cystic fibrosis. Am J Cliii Nutr 1980; 33:2281-86 28 Qumton PM. Chloride impermeability in cystic fibrosis. Nature 1983; 301:421-22 29 Cohen LF, di Sant’Agnese PA, FriedlanderJ. Cystic fibrosis and pregnancy: a national survey. Lancet 1980; 2:842-44 27

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