The Effect of Atropine Inhalation in “Irreversible” Chronic Bronchitis

I The

CLINICAL

Effect

“

INVESTIGATIONS

of Atropine I,,

#{149}

J. Marini,

Chronic

M.D.,#{176}* and

in

#{149}.*

#{149}

Irreversibue. John

Inhalation Bronchitis

S. Lakshminarayan,

M.D.,

F.C.C.P.

Fifteen patients with chronic bronchitis and airflow ohsfruction which was not improved by inhalation of isoproterenol (increase in forced exphatory volume in one second [FEy1] less than 15 percent) received an aerosol of atropine sulfate (0.05 mg/kg of body weight), In order to determine their response to an anticholinergic bronchodilator drug. The improvement over initial values for FEV1 at 15 mInutes following inhalation of isoproterenol and at 90 mInutes following inhalation of atropine averaged 5.9 percent and 19.2 percent, respectively (P < 0.01). Eleven of 15 patIents demon-

strated a 15 percent or greater increase in FEV1 following inhalation of atrophic, and six subjects demonstrated more than 25 percent Improvement. The maximum effect of atropine was observed at or later than 90 mInutes following inhalation In nine of 11 patIents who were responsive to atrophic. Minim2l systemic toxic effects resulted from inhalation of atrophic, although dryness of the mouth was frequenL In patients with chronic bronchitis, airflow obstruction resistant to isoproterenol may respond to inhalation of an aerosol of atrophic sulfate.

1nticholinergic

determine

drugs

agents years.’ tually

and

have

However,

are

effective

been

inhalation

abandoned

of the

impair

clearance

of

having

any

advantages,

mucociliary

retarded

by

mucus

atropine,1#{176}

may

production.’3 studies

little

even-

anticholinergic

that

it may

atropine

without with

experimental

and of afroabnormal

the

results

anticholinergic

of

aerosols

in patients

with

investigators

have

with information

$-syrnpathomimetic is available

of anticholinergic struction refractory

compounds to the

#{176}From the Respiratory Disease istration Hospital, and the Department of Medicine, Seattle. #{176}#{176}Fellow of the American Lung Manuscript received April 12; Reprint requests: Dr. Marini, Avenue South, Seattle 98114

CHEST, 77: 5, MAY,

compared

compounds is partially

chronic

1980

acirenergic

in patients or completely

whose re-

medications, concerning the

but effect

in patients -agothsts. In

with order

obto

AdininDivision, Washington,

Division, Veterans Respiratory

University

Disease

of

Association. revision accepted USPHS Hospital,

drug

July 3. 1131 14th

to

predicts

aerosols,

studied

patients

obstruction

an

adrenergic

nonresponsiveness

we

in

airflow

inhalation

the

with which

to effect

chronic did

not

of

bronimprove

of isoproterenol.

not Alis

nonresponsiveness

inhalation and

after

airways

that derivatives in patients with

effective

chitis

avail-

18

with anticholinergic obstruction to airflow versible

was

in normal

that

be particularly

bronchitis. Several

bronchodilator

This criticism may chronic bronchitis.

recent

if

many

secretions

Furthermore,

indicate

for

compared

clearance

clinical evidence suggests pine are well tolerated other

concern

bronchial

able $-adrenergic aerosols.9 be justified in patients with though

use

of atropine

because

major

bronchodilator

in clinical

MATERIALS

1)

METhODS

male patients with chronic airflow obstruction, (ratio of forced expiratory flow in one second over forced vital capacity [FEV1/FVC] less than 70 percent) which did not reverse significantly following inhalation of isoproterenol were studied. Significant response to the bronchodilator was defined as 15 percent or greater improvement in FEy1 15 minutes following the completion of ten inspiratory-capacity inhalations of a 1:1,000 solution of isoproterenol delivered from a compressor-driven nebulizer (Maximyst). The mean age of the patients was 63 years (range, 48 to 81 years). All subjects were current or former cigarette smokers, and all Fifteen

fulfilled

the

British

Medical

Research

Council’s

criteria

for

chronic bronchitis.’#{176} Patients with respiratory infections within the preceding month and those receiving propranolol were excluded. Of 13 patients in whom a detailed pharmacologic history was available, four used daily orally administered or inhaled p-agonists. None had received atropine by inhalation prior to this study, and all had performed spirometric tests on at least two previous occasions, including a screening trial of bronchodilator conducted on a day prior to the study. A single-blind sequential protocol was followed to ensure that each patient to isoproterenol pulmonary

was

tested

at a time when he was refractory significant diurnal variations in responsiveness to bronchodilators.

and to avoid

function

or

ATROPINE INHALATION IN CHRONIC BRONCHITIS 591

of atropine sulfate (9.6 mg/mI) was prepared from powdered atropine sulfate and 0.5 N saline solution, and the approximate number of breaths required to nebulize the solution

subject reported at midmorning of the testing day, having withheld all forms of theophylline and adrenergic medication for 12 hours, and informed consent was obtained. The patient was coached to cough and clear secretions before the study was begun. Ten minutes following control spirometric testing, an aerosol of isoproterenol hydrochloride (800 g) was administered, and spirometric testing was repeated 15 minutes after the final breath of medication. Thirty minutes Each

desired dose was calculated using the patient’s weight on the day of testing. The same number of breaths of placebo and atropine were given. At each time of testing, three forced spirograms were recorded with an automated spirometer (Systems Reearch Laboratories model M130), and the effort which resulted in the highest FEY1 was utilized for analysis. The forced expiratory flow rate occurring between 25 and 75 percent of the forced vital capacity (FEF 25-75%) was measured before and after inhalation, and these values were compared using the isovolume method. The blood pressure, pulse rate, and 60-second electrocardiogram were recorded five minutes following inhalation of isoproterenol and 15 minutes after inhalation of atropine. Spontaneous complaints, as well as responses to specific questions concerning urinary retention, visual blurring, palpitations, mental clarity, and dryness of the mouth, were recorded. Statistical comparisons were made using a two-

following inhalation of isoproterenol, a placebo aerosol of 0.5 N saline solution flavored with quinine sulfate to imitate the bitterness of atropine was administered, and spirometric testing was repeated after a 15-minute interval. An aerosol of atropine sulfate (0.05 mg/kg of body weight) was then delivered, and spirometric testing was done at 20, 50, 90, and 120 minutes following the final breath of medication. The timing of spirometric testing after inhalation of isoproterenol and atropine was chosen in order to measure the anticipated peak effects of both agents. For each patient, spirometric testing was performed by the same technician, who did not vary the coaching technique. The subjects were unaware of the nature and sequence of the tested drugs. Each aerosol was generated by a compressor-driven nebulizer (Maximyst) located 1 to 2 cm from the lips and was administered by multiple inspiratory-capacity breaths over a ten-minute period. Prior to the study, the average loss of weight from the nebulizer per inspiratorycapacity inhalation was determined by repeated gravimetric determinations on an analytical balance. The doses of isoproterenol and atropine administered were calculated on the basis of the number of inhalations given and the concentrations of the respective solutions. Medication was nebulized only during inhalation of the tested drug. A concentrated Table

1-Spirometric

Values

for

FVC

tailed

Student’s

15 mm

Initial

Subject

after Isoproterenol

for paired

data.#{176}

RESULTS

Data

on

displayed the FEy1

and

and

shown

When before

the

FVC

and

in Tables

percent

FEF

after

and

FEy1

1 and

improvement 25-75% to

Inhalation

for

2. For over is

graphically

compared

FVC

(percent predicted)

t-test

each

initial

patients tested

FEY1

initial

value,

of FVC, in

in

are aerosol

values

summarized for

the

all

Table

Figure the

FEy1

of Aerosols

L*

mm after Placebo

after Atropine

after Atropine

after Atropine

after Atropine

15

20

mm

50

mm

90

mm

120

mm

1

2.96

(79)

3.14

3.02

3.34

3.14

2.88

3.12

2

2.19

(80)

2.40

2.44)

2.60

2.51

2.60

2.65

3

2.68 (84)

2.71

3.24

3.55

3.44

3.45

3.48

4

1.41 (41)

1.64

1.57

2.26

2.25

2.18

2.08

5

3.25 (82)

3.32

3.25

3.36

3.60

3.57

3.54

6

2.47 (69)

2.48

2.32

2.65

2.57

2.53

2.54

7

2.69 (56)

2.81

2.98

3.19

3.31

3.30

3.37

8

3.96 (89)

4.45

4.32

4.72

4.79

4.75

4.87

9

2.64

(58)

2.74 2.27

2.70

3.07

3.39

3.10

3.36

2.45

2.57

2.70

2.67

2.75

10

2.17 (51)

11

2.34

(55)

2.14

2.21

2.52

2.53

2.57

2.60

12

3.68

(85)

3.22

3.35

3.49

3.75

3.71

3.43

13

1.85

(48)

1.93

1.87

2.09

1.87

2.16

1.98

14

3.02

(83)

3.21

3.07

3.14

3.09

2.99

3.04

15

3.47

(82)

3.37

3.32

3.31

3.26

3.36

3.04

2.79±0.70

2.82±0.63

Mean

±

5A11 values

592

SE

2.72±0.69 are recorded

as STPD.

MARINI, LAKSIIMINARAYAN

Dose

of isoproterenol

was 800pg,

3 1.

3.08±0.71

and dosage

3.08±0.71 of atropine was

3.05±0.67 0.05

3.06±0.70

mg/kg.

CHEST, 77: 5, MAY, 1980

Table

2-Spirometrie

Values

for

FEV1

before

and

after

FEY1,

miii after

Initial

15

(percent Subject

15

Isoproterenol

predicted)

of

Aerosols

L*

20 miii

50

mmn after

mm

after

after

after

Placebo

Atropine

Atropine

120 miii

90

after

Atropune

Atropine

1

1.85

(62)

1.84

1.77

2.13

1.90

1.80

1.85

2

1.06

(52)

1.12

1.11

1.26

1.21

1.19

1.24

3

1.03

(41)

1.15

1.32

1.57

1.47

1.61

1.45

4

0.65

(24)

0.70

0.67

0.82

0.81

0.78

0.82

5

1.85

(59)

1.95

1.87

2.01

2.05

2.14

2.02

6

1.26

(48)

1.36

1.35

1.54

1.52

1.54

1.58

7

1.44

(37)

1.64

1.68

1.75

1.75

1.77

1.75

8

2.47

(71)

2.81

2.67

3.13

3.05

3.25

3.27

9

1.32

(37)

1.37

1.30

1.72

1.90

1.83

1.93

10

0.85

(25)

0.95

1.00

1.07

1.15

1.16

1.24

11

1.63

(49)

1.52

1.52

1.81

1.89

1.89

1.91

12

2.57

(72)

2.51

2.40

2.62

2.80

2.73

2.67

13

0.64

(21)

0.64

0.58

0.61

0.62

0.73

0.67

14

1.67

(58)

1.79

1.67

1.70

1.64

1.65

1.62

15

1.37

(41)

1.47

1.40

1.42

1.42

1.34

1.28

1.44

±0.58

Mean 5All

±

SE

values

are

improved

recorded

1.52

as STPD.

by greater

than

Dose

±0.61

1.49

of isoproterenol

15 percent

after

provement

ranged

minutes

following

showed

a lower

from

46

to

inhalation FEy1

56

percent.

than

placebo; and at all times of testing pine, the mean percent improvement FEY1

over

the

than

initial

corresponding

proterenol bo, are

values

(P

rather

<

than

considered results are not after inhalation provement value, was

<

FVC. The FEY1 following onstrated

to be

the

the

placebo, different

0.01).

Similar

at

occurred

values

which was

FEY1

inhalation maximum

of FEY1

and

FYC,

13.6 percent. Both the improvement

maximum not

uniform

improved

of atropine. improvement

CHEST,77: 5, MAY, 1980

the initial with the

(5.9 obtained

by

percent, with

improvement among

were ob-

the

sage

six 25

of

Testing

at

hours

120 after

continued

to

improvement After Over

Percentage

Improvement

over

inhalation

of

Initial

Values (±

SE)

-.‘.-

FVC

15 mm after msoproterenol*

patients

Improvement

Mean

six

Two

percent minimal.

,_

of

and

of atropine.

were

±0.66

0.05 mg/kg.

atropine,

effects

3-Percen Time

for

inhalation

Spirometnc

isoplace-

with compared

were

Table

higher the

of isoproterenol results

at least FEY1.

atropine, the different; 90 minutes the mean percent im-

compared and, was from

of

Adverse

1.69

±0.67

at 90 minutes,

demonstrate their initial

after

control

of atropine,

inhalation

time

values

substantially

after

jects whose

initial

in FEy1, 19.2 percent

value after significantly served

If the

three

after

1.69

was

inhalation

atroand

following

of atropine

2).

of the

significantly

improvement

0.01). the

was

and dosage

±0.65

im-

Twenty

following in FVC

1.68

minutes

no patient

inhalation

after

800ag,

±0.65

at 50 minutes,

inhalation

of atropine,

1.68

±0.57 was

of atropine in 11 subjects (patients 1 to 11; Table In three patients (patients 3, 9, and 10), this

P

miii

Inhalation

FEy1

FEF25-75%

3.1 ± 1.9

5.9 ± 1.5

8.5 ±4.0

3.9 ±2.2

4.1

0.5

15 miii after

placebo

±2.6

±6.1

mm after

20

atropune** 50

mm

t

17.5 ± 3.7t

19.9 ±7.5

±4.3f

17.7

±3.9t

20.0

±6.7

± 3.9t

19.2

±4.2t

19.2

±9.3

18.7

±4.5t

30.6

±9.01:

14.7

±4.1

14.5

14.5

after

atropi.ne**

90 mm after the

in 11 sub-

at least 15 percent One subject demat 20 minutes, one

atropune**

120 miii after 13.9±4.11:

atropine**

5Dose

of 800ag.

**Dosage

of 0.05

tP

<0.01,

1:P <0.02,

mg/kg.

compared

to isoproterenol.

compared

to

isoproterenol.

ATROPINE INHALATION IN CHRONIC BRONCHITIS 593

6050.. S S

.

4O . S

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4

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Placebo

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Atropine

. #{149}

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S

S

I

‘

0

I

‘

30

I

‘

60

I

‘

90

‘

I

‘

120

‘

I

‘

180

150

Minutes Ficuna

1. Percent

improvement

in FEy1

initial

over

values.

Iso,

Isoproterenol.

equivalent

or

superior

bronchodilator

atropine, 12 patients complained of dryness of the mouth, which lasted for the duration of the study. The mean rise in heart rate was nine beats per minute (range, 0 to 35 beats per minute) following

agents

inhalation

the

agents when airflow obstruction is refractory to inhaled adrenergic medication. Klock and associates’3 evaluated the effects of inhaled atropine sulfate and isoproterenol hydrochloride in 15 patients with

DIscussIoN

improved airflow with both agents, four patients responded to neither drug, and four patients improved only with atropine. Although these results suggest that some patients with chronic bronchitis may respond selectively to atropine, Klock et aP3 do

(range, tion

of

of isoproterenol -10

to 8 beats

atropune.

and

two

beats

per minute)

For

both

per

minute

following

agents,

no

inhala-

detectable

mean blood pressure or in the number of premature contractions recorded during a one-minute ECG. Three patients reported a sensation of “lightheadedness” lasting approximately one hour following inhalation of atropine. changes

The

occurred

current

in

study

demonstrates

that

an

unex-

pectedly high proportion of patients with chronic bronchitis and airflow obstruction refractory to inhaled isoproterenol respond favorably to inhalation of atropine

and

patients. cholinergic ble

of

the

response

work

tone

obstruction

result

that

Previous

is an important in chronic

heightened

is marked

has suggested bronchitis,

perhaps

irritant-receptor the

tients with tion which

and

aerosols

and

improves

have

bronchitis

effects compounds

significantly

concluded

594 MARINI, LAKSHMINARAYAN

of reversi-

that

airflow with

as the

patients.’-8

in such

contrast,

In

available

not

comparatively

regarding

chronic

stress

this

conducted

tests

Cavanaugh

sponse

and

asthmatic

children

dose

achieve a maximum administered by

anticholinergic

of 0.05

(dosimeter).

atropine has

not

and

mg/kg

been

adult

the

patients

determined,

of

in 20 average

is necessary

optimal 0.05

an

when the metering dose

with

60

dose-re-

sulfate that

weight

or

than

the

atropine

response a precision

the

number

examined

of body

Since

for

later

a greater detected.

determined

had

of atropine

function

of inhaled

patients

that

1 mg

Cooper22

relationship

seven

possible

minutes after administration, responders would have been

reflexes.2’

obstruc-

is

than

of pulmonary

of sympain paadrenergic

It

is

anticholinergic

that

noted

more

information

of

efficacy

and

point.

used

little

the

bronchitis

investigators

increased

mediator

Recent reports have compared thomimetic and anticholinergic

chronic

in some

that

are

agents

chronic

mg/kg

was

to

aerosol is device of

inhaled

bronchitis nebulized

CHEST, 77: 5, MAY, 1980

in the present delivered sent

study.

to the

The

precise

airways

a submaximal

amount

is unknown

dose,

since

of atropine

and

may

did

not

we

sistance

in

Department

repre-

Hospital,

use

performing tests of pulmonary function and of Pharmacy of the Veterans Administration Seattle, for preparation of the tested medications.

a

dosimeter.

REFERENCES

was

Isoproterenol

the

because

it is extensively

function

laboratories

action

and

(60 trial

without

testing

of isoproterenol of its peak

an

observed

in order

dose

the

other in the had

Another to

atropine

as

suggested

jects

dose

three

for

be

by

by

patients

20 beats

selective

per

to

since

a minority

therapy,

this

of

our

the

present

study

the

absolute

sub-

13

seems

flow often

rate seen after inhalation modest in the patients with

tion.

Nevertheless

small atically

these

of the

rates

Although

and

determined, that

many

not

improve

the

optimal

safety the

rivatives

dosage,

of aerosols results

patients

a

patients

may

be

symptom-

significantly

15

with

with

be

study

who

an adrenergic

16

do

17

aerosol

of atropine.

Tests

or one

considered

to be establish

bronchitis

atropine

therefore

effective-

remain

present

chronic

inhalation

function should

long-term

of atropine

of the

with

do so following

pulmonary

of

of its dein such

18

Raymond

Morris,

and

CHEST, 77: 5, MAY, 1980

We

thank

Ms.

Mr.

Bruce

Thomas

Claudia for

Baigehnan,

French, their

atropine

CF:

Aerosol

SCH-1000:

Rev

Ghazarshahi

S, et

effects

of

Dis

Respir al:

Com-

SCH-1000

bronchial

with

asthma.

Ann

Al-

Atropine

methonitrate

and

2:1019-1021, Thursby-Pelham DC:

atropine

methonitrate

given

comparative

study.

W,

S:

Br

isoprenaline

1962 Some adrenergic

Lancet

by

inhalation

J

Med

for

1:1018-1021,

Chodosh

Bronchodilator

action

of

the

as-

on

20

sputum

production.

Thorax

30:543-547,

J, Reid L: The effect of the human bronchial

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19

ACKNOWLEDGMENTS:

MCS, A

broncho1975

Am

with

pa-

1976

asthma.

and

Reed

RG,

patients

DA:

bronchial

tropium

pa-

tients.

Mr.

14

atropine was most obstruc-

compromised

in flow

in

beneficial.

ness,

will

in

improvement

increment

in

asthma:

remote. In

GA,

antigen

asthmatic

anticholinergic

112:823-828,

bronchodilating

36:223-230,

1975 12 Sturgess activity

3-adrenergic

possibility

the

of in

1972

bronchodilator.

Chamberlain

of

to chronic use of /3-agonists, in vitro and clinical experi-

other

such

DoPico

1952

Inhibition atropine

new

Dis

1975 T, Townley

of

drugs

responsiveness

tachyphylaxis

however,

received

WW,

A

Respir

Effects in man.

anticholinergic drug, ipratropium bromide (SCH-1000), as an aerosol in chronic bronchitis and asthma. Chest 71:324-328, 1977 9 Herxheimer H: Atropune cigarettes in asthma and emphysema. Br Med J 2:167-171, 1959 10 Yeates DB, Aspin N, Levison H, et a!: Mucociiary tracheal transport rates in man. J Appi Physiol 39:487493, 1975 11 Lopez-Vidriero MT, Costello J, Clark TJH, et a!: Effect

amount used conducted of our

WM:

RM:

resistance

1964

or exceeds

exceeding

139:198-211,

32:823-827,

anticholinergic

7 Kennedy

8

determined

Ther

by

Physiol Rev

airway

Gold

SCH-1000:

Am

Storms

in

of de-

nebulized

approaches

rate

secondary

ments;2527

6

its administration.

may

NJ:

lergy

is

in mode

and is twice the of the bronchodilator

explanation

stimulation

Gross

Appi

isoproterenol

explanation

determined

In addition,

following

J

parison

used was not suffiresponse, but this is

single

in pulse

im-

to atropine

possible

we used

laboratory.

tients.

An

mechanisms are alternative

differences

effective

increases

minute

4

SP,

McCredie

Jr, the

bronchoconstriction

dilator.

the

in the

response

One

for

investigators23 routine trials

in our

cholinergic there

gravimetrically

maximally

Galant

5 Vlagopoulos difference

selective

of isoproterenol

the

3

FW on

Pharmacodyn

DYC,

111:419-422,

patients.

Allowing

livery,24

with

Int

Yu

Lovejoy

microaerosols

induced

broncho-

to coincide

of isoproterenol a near maximum

to elicit

Arch 2

sequen-

of its

overlap

of

of atropine. Spirometric 15 minutes following adminis-

the

in our

unlikely.

to

duration

a brief

L,

of atropine

that

endogenous

for

that the amount

cient

short

permitted

portance of adrenergic and in mediating bronchospasm,

explanations

1 Dautrebande

action.23

from

Apart

tested

pulmonary

responsiveness its

significant

tration time

agent

in clinical

because

to 90 minutes)

effect with was conducted

dilator

$-adrenergic used

to determine

bronchodilators tial

the

bromide asthma.

Medical

Br

and Med

Research of

demiologic

purposes. GW,

in 1975

Council

classification Snedecor

salbutamol

J 1:430-432,

chronic Cochran

of

Great

bronchitis Lancet WG:

chronic Britain:

for

1:776, Statistical

clinical

bronchitis Definitionand

epi-

1965 Methods.

ATROPINE INHALATION IN CHRONIC BRONCHITIS

Ames,

595

21

structive

airway

J Clin

disease.

Invest

Comparison of dosage strength, and method of administration. J Allergy Clin Immunol 63:11-121, 1979 25 Douglas JS, Lewis AJ, Ridgeway P. et al: Tachyphylaxis to p-adrenoreceptor agonists in guinea pig airway smooth muscle in vivo and in vitro. Ear J Pharmacol 42:195-205, butaline

Iowa, Iowa State University Press, 1967, p 91 Simonsson BC, Jacobs FM, Nadel JA: Role of the tonomic nervous system and the cough reflex in increased responsiveness of airways in patients with

ob-

46:1812-1818,

1967

22

Cavanaugh

Dose 517-524,

MJ,

response

Cooper DM: Inhaled atropine characteristics. Am Rev Respir

1977

26

BP, Noland BJ, Jenne JW: Desensitization of bronchial smooth muscle to fl-receptor agonists. Proc West Pharmacol Soc 20:25-31, 1977 27 Holgate ST, Baldwin CJ, Tattersfield AE: p-adrenergic agonist resistance in normal human airways. Lancet 2:375-

RW,

Avner

human

MH Jr. Kane C: Dose to inhaled isoproterenol. 111:321-325, 1975

Weber

sulfate: 114:

Dis

1976

23 Williams asthma 24

in asthmatics:

schedule,

authe

of patients with

response

Am

Nelson

Rev

HW:

Respir

Dis

Aerosolized

ter-

Petty

WE,

5th

Canadian Summer Workshop in Electrocardiography

The the

J. L. St.

Rogers

Hotel

Heart

Foundation

MacDonald,

For

Marriott.

Petersburg,

will present

Edmonton,

Alberta,

contact

information,

Florida

377,

July

Rogers

1977

the 5th Canadian Summer 19-22, under the direction Heart Foundation, 601 12th

Workshop at of Dr. Henry Street

North,

33705.

Occupational

Respiratory

Protection

The Rocky Mountain Center for Occupational and Environmental Health at the University of Utah will sponsor this course (NIOSH course 593) on the following dates: July 7-11 in Las Vegas; August 25-29 in Park City, Utah; October 20-24 in Salt Lake City. For information, contact Ms. Katharine Blosch, Building 112, University of Utah, Salt Lake City 84112.

What’s The Pediatric

Niagara Hospital,

596

State Lung

Falls, 219

University Disease,

New Bryant

MARINI, LAKSHMINARAYAN

New of New July

in Pediatric York

10-11

York. Contact Street, Buffalo

at Buffalo

at the Niagara

Ms.

Rayna

Lung

Disease

will present the course, What’s New in Falls International Convention Center, Dutton, CME Coordinator, Children’s

14222.

CHEST,

77: 5, MAY, 1980